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NCI CANCERLIT® Search: Kidney (Renal Cell) Cancer - August 2002
National Cancer Institute®
Ultima Vez Modificado: 1 de agosto del 2002
- Differential gene expression in renal-cell cancer.
- Impact of surgery on survival in palliative patients with metastatic colorectal cancer after first line treatment with weekly 24-hour
- Evaluation of sonographically guided percutaneous core biopsy of renal masses.
- Update on pathologic staging of renal cell carcinoma.
- Renal cell carcinoma-associated G250 methylation and expression: in vivo and in vitro studies.
- Minichromosome maintenance protein 2 expression in normal kidney and renal cell carcinomas: relationship to tumor dormancy and potential
- Renal cell carcinoma and occupational exposure to chemicals in Canada.
- [Studies on the interaction between interleukin-6 and human renal cell carcinoma cell line GRC-1]
- Quantitative analysis of gene expressions of vascular endothelial growth factor-related factors and their receptors in renal cell carcinoma.
- Functional and gene expression analysis of the p53 signaling pathway in clear cell sarcoma of the kidney and congenital mesoblastic nephroma.
- VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma.
- Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours.
- Alterations of the DNA repair gene OGG1 in human clear cell carcinomas of the kidney.
- hOGG1 gene alterations in human clear cell carcinomas of the kidney: effect of single mutations in hOGG1 gene on substrate specificity of the
- Renal cell carcinoma related novel gene, GYLZ-RCC18: cloning and functional studies.
- Numerical chromosomal aberrations in papillary renal cortical tumors: relationship with histopathologic features.
- Renal cell carcinoma in the solitary kidney: an analysis of complications and outcome after nephron sparing surgery.
- Primary apoptosis as a prognostic index for the classification of metastatic renal cell carcinoma.
- Re: Percutaneous radio frequency ablation of small renal tumors: initial results.
- Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: a study of incidence and its association with
- [Laparoscopic tumor nephrectomy]
- [Long-term results of organ-preserving surgeries for renal cell carcinoma]
- Cryptic t(12;15)(p13;q26) producing the ETV6-NTRK3 fusion gene and no loss of IGF2 imprinting in congenital mesoblastic nephroma with trisomy
- Clinical significance of allelic loss of chromosome region 5q22.3 approximately q23.2 in nonpapillary renal cell carcinoma.
- Bladder neoplasms after nephroureterectomy: does the surgery of the lower ureter, transurethral resection or open surgery, influence the
- Disruption of a novel MFS transporter gene, DIRC2, by a familial renal cell carcinoma-associated t(2;3)(q35;q21).
- [Multi-slice CT in the planning of nephron-sparing interventions for renal cell carcinoma: Prospective study correlated with histopathology]
- Between the Scylla and Charybdis of peptide radionuclide therapy: hitting the tumor and saving the kidney.
- 131 I-cG250 monoclonal antibody immunoscintigraphy versus [18 F]FDG-PET imaging in patients with metastatic renal cell carcinoma: a comparative
- Prognostic value of nuclear grading in patients with intracapsular (pT1-pT2) renal cell carcinoma. Long-term analysis in 213 patients.
- A phase II trial of intravenous gemcitabine and 5-fluorouracil with subcutaneous interleukin-2 and interferon-alpha in patients with
- Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma.
- Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based
Table of Contents
1
UI - 12080328
AU - Skubitz KM; Skubitz AP
TI -
Differential gene expression in renal-cell cancer.
SO - J Lab Clin Med 2002 Jul;140(1):52-64
AD - Department of Medicine, University of Minnesota Medical School,
Minneapolis, USA.
Renal-cell carcinoma (RCC) is an important cause of morbidity and
mortality, and its incidence has been increasing. Malignant
transformation is thought to be associated with changes in the
expression of several genes, and this alteration in gene expression is
believed to be critical to the development of the malignant phenotype.
In this study, the expression of about 60,000 genes/expressed sequence
tags in clear-cell RCC, normal kidney, and a set of diseased
nonmalignant kidneys was determined with the use of the Affymetrix
microarray technique, and differences in gene expression were analyzed.
Many genes were found to be differentially expressed in these two sample
sets. The genes that were expressed greater than four times more in RCC,
those expressed only in RCC, and those expressed greater than two times
more in RCC and also expressed in a limited number of other tissues were
analyzed for their expression in a variety of other normal and diseased
tissues. Some of the genes identified were overexpressed only in RCC
among the tissues examined, and some were overexpressed in several other
malignant tissues in addition to RCC. Other genes were overexpressed in
RCC compared with normal kidney but were also overexpressed in diseased
nonmalignant kidney or a variety of other normal tissues. All of the RCC
samples could be clustered together, separate from the normal and
diseased kidney samples, with the use of the Eisen clustering technique
and a set of 50 genes. The observed changes in gene expression in RCC
should help further the understanding of the biology of RCC and may be
useful in diagnosis, treatment, and imaging.
2
UI - 11843250
AU - Wein A; Riedel C; Kockerling F; Martus P; Baum U; Brueckl WM; Reck T;
TI -
Ott R; Hansler J; Bernatik T; Becker D; Schneider T; Hohenberger W; Hahn
EG
Impact of surgery on survival in palliative patients with metastatic
colorectal cancer after first line treatment with weekly 24-hour
infusion of high-dose 5-fluorouracil and folinic acid.
SO - Ann Oncol 2001 Dec;12(12):1721-7
AD - Department of Internal Medicine I, Friedrich-Alexander-University
Erlangen-Nuremberg, Erlangen, Germany.
Axel.Wein@med1.imed.uni-erlangen.de
BACKGROUND: In palliative first-line treatment of colorectal cancer, the
secondary resection of distant metastases after downstaging has
constantly gained in importance. The objective of this prospective study
was to examine the tumor response rate, the toxicity, the median
survival time and the prognostic impact of metastatic resection after
downstaging of consecutively enrolled patients with primary
nonresectable colorectal cancer treated with once weekly 24-hour (24-h)
infusion of high-dose 5-fluorouracil (5-FU) and folinic acid. PATIENTS
with primary nonresectable metastases were recruited for a prospective
phase II study. The patients received in out-patient care 500 mg/m2
folinic acid in the form of a 1-2-hour infusion followed by 2600 mg/m2
5-FU administered as a 24-h infusion once weekly. One treatment cycle
comprised six weekly infusions followed by a two week rest. Three cycles
were administered, and in the event of complete remission (CR) or
partial remission (PR) and good tolerability, a fourth cycle was
undertaken. Thereafter, the possibility of performing a curative
metastatic resection was investigated. RESULTS: Of the 53 patients
treated, 7 showed a CR (13%), 15 patients a PR (28%), 26 patients stable
disease (SD) (49%), and 5 patients progressive disease (PD) (10%). As
the main symptom of toxicity, diarrhea (CTC grade 3 + 4) was observed in
11 patients (21%), followed by leucocytopenia (CTC grade 3 + 4) in 2
patients (4%), and the hand-foot syndrome in 1 patient (2%). The median
survival time was 17 months with a median follow-up of 41 months (range:
28-59 months). In 9 patients (17%), a secondary metastatic resection was
considered; in 6 patients (11%) curative resection was performed, and 4
patients (8%) showed no evidence of disease for at least three years.
CONCLUSION: In this phase II study, we have been able to show
prospectively that, after downstaging by palliative treatment using a
weekly 24-h infusion of high-dose 5-FU and folinic acid, secondary
curative metastatic resection was technically feasible in 11% of the
patients. For some of these patients, long-term survival is therefore
possible. Secondary metastatic resection should be carried out in close
interdisciplinary cooperation, and should be further investigated in
prospective phase III studies.
3
UI - 12130435
AU - Caoili EM; Bude RO; Higgins EJ; Hoff DL; Nghiem HV
TI -
Evaluation of sonographically guided percutaneous core biopsy of renal
masses.
SO - AJR Am J Roentgenol 2002 Aug;179(2):373-8
AD - Department of Radiology, University of Michigan Medical Center, 1500 E.
Medical Center Dr., Taubman Center 2910R, Ann Arbor, MI 48109-9723, USA.
OBJECTIVE: Our objective was to determine the utility of sonographically
guided percutaneous core biopsy to evaluate renal masses. MATERIALS AND
METHODS: We conducted a retrospective analysis of our imaging-guided
sonographically guided percutaneous core biopsies of renal masses in 26
patients. From two to five specimens were obtained from a single mass in
each patient using an 18-gauge automated biopsy system. We examined the
patients' medical records, pathology results, and imaging studies. Core
biopsy results were compared with surgical pathology (n = 6) or clinical
follow-up (n = 20). RESULTS: All biopsies provided sufficient material
for analysis. Biopsy findings were positive for malignancy in 19 (73%)
of 26 masses. Histologic diagnoses included renal cell carcinoma were (n
= 11), metastasis (n = 3), lymphoma (n = 2), and transitional cell
carcinoma (n = 2). Specific cell type characterization could not be made
on one biopsy, but the specimens were highly suspicious for malignancy.
Biopsy revealed seven (27%) of 26 benign diagnoses: oncocytoma (n = 3),
angiomyolipoma (n = 2), and fibrosis (n = 2). The average follow-up
period for patients with benign diagnoses was 10 months. One case of
surgically proven necrotic pyelonephritis was mischaracterized as
fibrosis at core biopsy. Sonographically guided percutaneous core biopsy
of renal masses showed a sensitivity of 100% and a specificity of 100%
for the diagnosis of malignancy. The core specimens yielded a specific
diagnosis in 92% (24/26) of masses. No immediate complications occurred
after the procedure. One patient developed a pseudoaneurysm that
presented 3 months after the biopsy. CONCLUSION. Sonographically guided
percutaneous core biopsy is a reliable and accurate method for
evaluating renal masses.
4
UI - 12137811
AU - Gettman MT; Blute ML
TI -
Update on pathologic staging of renal cell carcinoma.
SO - Urology 2002 Aug;60(2):209-17
AD - Department of Urology, Mayo Clinic, Rochester, Minnesota 55905, USA.
5
UI - 12137853
AU - Grabmaier K; de Weijert M; Uemura H; Schalken J; Oosterwijk E
TI -
Renal cell carcinoma-associated G250 methylation and expression: in vivo
and in vitro studies.
SO - Urology 2002 Aug;60(2):357-62
AD - Experimental Urology, Department of Urology, University Medical Center
Nijmegen, Nijmegen, The Netherlands.
OBJECTIVES: In renal cell carcinoma (RCC) cell lines, expression of the
RCC-associated antigen G250 correlates with hypomethylation of the
investigated CpG dinucleotides in the G250 promoter region, despite the
absence of a CpG island. To gain insight into the molecular mechanism
leading to G250 expression in vivo, we ascertained whether this
correlation between G250 gene expression and the methylation status of
the G250 gene also existed in primary RCC and normal kidney tissue.
METHODS: G250 mRNA and protein expression was determined by reverse
transcriptase-polymerase chain reaction, fluorescence activated cell
sorting analysis, and immunohistochemistry in 15 RCC cell lines and 13
paired primary RCC/normal kidney tissue specimens. The methylation
status of the G250 gene was determined by bisulfite genomic sequencing.
RESULTS: RCC cell lines revealed a clear correlation between G250
expression and hypomethylation. In contrast, no hypomethylation was
observed in primary RCC compared with normal kidney tissue. The CpG
dinucleotides investigated were generally completely methylated in RCC,
as well as in normal kidney tissue. Furthermore, a primary culture of
RCC tissue revealed increasing hypomethylation of the G250 gene in
successive passages, suggesting that the G250 hypomethylation observed
in vitro is tissue culture induced. CONCLUSIONS: The methylation status
of the G250 gene correlated with G250 expression in vitro but not in
vivo.
6
UI - 11948116
AU - Rodins K; Cheale M; Coleman N; Fox SB
TI -
Minichromosome maintenance protein 2 expression in normal kidney and
renal cell carcinomas: relationship to tumor dormancy and potential
clinical utility.
SO - Clin Cancer Res 2002 Apr;8(4):1075-81
AD - Anatomical Pathology, Canterbury Health Laboratories, Christchurch
Hospital, Christchurch, New Zealand 8001.
PURPOSE: A major problem in the management of patients with renal cell
carcinoma is predicting tumor behavior. In the search for more accurate
markers of prognosis, tumor cell proliferation has been investigated.
These studies have mostly used antibodies directed against Ki-67 or
proliferating cell nuclear antigen and have given conflicting results,
findings that are likely because of a combination of specificity and
methodological differences. Minichromosome maintenance (Mcm) proteins
are a series of closely related proteins that are components of the
prereplicative complex. The Mcm proteins are essential for initiating
eukaryotic DNA replication and serve as useful markers of proliferating
cells. EXPERIMENTAL DESIGN: The aims of this study were to determine the
frequency and pattern of Mcm2 expression by immunohistochemistry in
normal kidney (n = 10) and renal tumors [n = 56; clear cell n = 36;
chromophil (papillary) n = 7; oncocytoma n = 5; and transitional cell
carcinoma n = 8], compare its sensitivity to the established
proliferation marker Ki-67, examine for differences in tumors derived
from stable and labile epithelial cell populations in the kidney, and
assess the relationship of Mcm2 proliferation to clinicopathological
characteristics of kidney tumors. In addition, to additionally
investigate the issue of tumor dormancy we wished to assess the
relationship between Mcm2 labeling index (LI) and the angiogenic factors
angiopoietin-1 (Ang) and Ang-2. RESULTS: In normal tissues, Mcm2 nuclear
labeling was identified in both glomeruli (LI median 0.35%; range 0-1.7)
and renal tubules (LI median 0.3%; range 0.1-2.9%). In tumors Mcm2
labeling was predominantly at the periphery with LIs ranging from
0.2-91.5%, which was significantly greater than Ki-67 LI (0.2-40.5%; P <
0.001). Mcm2 LI was also significantly higher in tumors derived from a
labile epithelium (transitional cell carcinomas) than a stable
epithelium (renal cell carcinomas; P = 0.013). A significant association
was also demonstrated between Mcm2 LI and tumor grade (P = 0.0006), and
angiogenic phenotype (defined by Ang expression; P = 0.03) but not with
patient age (P = 0.84), patient sex (P = 0.25), tumor size (P = 0.74),
or stage (P = 0.33). Furthermore, although not significant, a survival
analysis demonstrated that 100% of patients with a low Mcm2 LI survived
compared with 84% of those with a high Mcm2 LI over the follow-up period
(up to 53.2 months; P = 0.14). CONCLUSIONS: This is the first study
examining Mcm2 protein in normal and tumor kidney samples, and the first
to perform histological subgroup analysis. It shows that Mcm2 is a
superior marker to Ki-67 in the assessment of cell cycle entry in
histological archival material and that normal kidney has a subset of
cells within the glomerular and tubular compartments that are in cycle.
It demonstrates that the frequency of cells in cycle in tumors formed
from stable or labile epithelial populations mirrors that in the
nonneoplastic epithelium. This study additionally demonstrates that the
number of cells in cycle in tumors is limited by the angiogenic
phenotype and supports animal models that show angiogenesis determines
the likelihood of tumor dormancy. Additional study to confirm the
clinical utility of Mcm2 as a prognostic marker is now indicated.
7
UI - 12063361
AU - Hu J; Mao Y; White K
TI -
Renal cell carcinoma and occupational exposure to chemicals in Canada.
SO - Occup Med (Lond) 2002 May;52(3):157-64
AD - Surveillance & Risk Assessment, Centre for Chronic Disease Prevention
and Control, Population and Public Health Branch, Health Canada, Ottawa,
Ontario, Canada..
This study assesses the effect of occupational exposure to specific
chemicals on the risk of renal cell carcinoma in Canada. Mailed
questionnaires were used to obtain data on 1279 (691 male and 588
female) newly diagnosed, histologically confirmed renal cell carcinoma
cases and 5370 population controls in eight Canadian provinces, between
1994 and 1997. Data were collected on socio-economic status, smoking
habit, alcohol use, diet, residential and occupational histories, and
years of exposure to any of 17 chemicals. Odds ratios (ORs) and 95%
confidence intervals (CIs) were derived using unconditional logistic
regression. The study found an increased risk of renal cell carcinoma in
males only, which was associated with occupational exposure to benzene;
benzidine; coal tar, soot, pitch, creosote or asphalt; herbicides;
mineral, cutting or lubricating oil; mustard gas; pesticides; and vinyl
chloride. Compared with no exposure to the specific chemical, the
adjusted ORs were 1.8 (95% CI = 1.2-2.6), 2.1 (1.3-3.6), 1.4 (1.1-1.8),
1.6 (1.3-2.0), 1.3 (1.1-1.7), 4.6 (1.7-12.5), 1.8 (1.4-2.3) and 2.0
(1.2-3.3), respectively; an elevated risk was also associated with
exposure to cadmium salts and isopropyl oil. The risk of renal cell
carcinoma increased with duration of exposure to benzene, benzidine,
cadmium, herbicides and vinyl chloride. Very few females were exposed to
specific chemicals in this study; further research is needed to clarify
the association between occupational exposure to chemicals and renal
cell carcinoma in females.
8
UI - 11798778
AU - Xi Z; Yu L; Guo Y
TI -
[Studies on the interaction between interleukin-6 and human renal cell
carcinoma cell line GRC-1]
SO - Zhonghua Yi Xue Za Zhi 2000 Apr;80(4):308-11
AD - Institute of Urology, The 1st Hospital of Beijing Medical University,
Beijing 100034, China.
OBJECTIVE: To demonstrate the effects of IL-6 on the renal cell
carcinoma cell line GRC-1. METHODS AND RESULTS: Immunocytochemical
staining and RT-PCR analysis indicated that this cell line could express
IL-6 both on mRNA and protein levels. Secretion of IL-6 in this cell
line was 465 pg/ml, which was identified by ELISA assay. By RT-PCR
analysis, we found that GRC-1 expressed IL-6 receptor system including
IL-6 mRNA and gp130 mRNA. The rhIL-6 did not stimulate the growth of
GRC-1 while the neutralizing antibody did not inhibit its growth. For
further identification of the effect of IL-6 on GRC-1 cells, we
introduced an antisense IL-6 RNA into GRC-1 cells. Thereafter, the
lowered expression of IL-6 mRNA was observed by Northern blot, and the
secretion of IL-6 was reduced to 250 pg/ml. But there were no
significant growth-inhibitory effects on GRC-1 cells. CONCLUSION:
Although GRC-1 could express IL-6, IL-6 R and gp130, the rhIL-6 and IL-6
neutralizing antibody or transducing antisense IL-6 RNA could not change
the growth of GRC-1 cells significantly. These results suggest that it
is not likely for IL-6 functioning as an autocrine growth factor for
GRC-1.
9
UI - 11846206
AU - Tsuchiya N; Sato K; Akao T; Kakinuma H; Sasaki R; Shimoda N; Satoh S;
TI -
Habuchi T; Ogawa O; Kato T
Quantitative analysis of gene expressions of vascular endothelial growth
factor-related factors and their receptors in renal cell carcinoma.
SO - Tohoku J Exp Med 2001 Oct;195(2):101-13
AD - Department of Urology, Akita University School of Medicine, Japan.
Vascular endothelial growth factor (VEGF)-related factors are believed
to regulate angiogenesis, an essential event in the growth of solid
tumors. In this study, we investigated the expression of VEGF-related
factor genes (VEGF, VEGF-B, and VEGF-C) and their receptor genes
(VEGFR-1 and VEGFR-2) in renal cell carcinoma (RCC). There were
significant differences in the expression level of VEGF, VEGFR-1 and
VEGFR-2 between RCC and the corresponding normal renal tissue. The
expression level of VEGF in the tumor tissue significantly correlated
with those of VEGFR-1 and VEGFR-2. Expression levels VEGF-B and VEGF-C
genes were not significantly different between RCC and normal renal
tissue. A moderate to high protein expression for VEGF, VEGFR-1, and
VEGFR-2 was observed in both the tumor cells and the endothelial cells,
whereas the protein expression was low for VEGF-B and VEGF-C. The
present results suggested that VEGF and its receptors VEGFR-1 and
VEGFR-2 cooperates to play a crucial role in the angiogenesis of RCC,
while VEGF-B and VEGFR-C may not. Furthermore, since VEGFR-1 and VEGFR-2
proteins were expressed in the tumor cells as well as in the endothelial
cells, these receptors may also be responsible for the progression of
RCC.
10
UI - 12007018
AU - Brownlee NA; Hazen-Martin DJ; Garvin AJ; Re GG
TI -
Functional and gene expression analysis of the p53 signaling pathway in
clear cell sarcoma of the kidney and congenital mesoblastic nephroma.
SO - Pediatr Dev Pathol 2002 May-Jun;5(3):257-68
AD - Department of Pathology and Laboratory Medicine, Medical University of
South Carolina, 171 Ashley Avenue, Charleston, SC 29425, USA.
Mutation of p53 has been implicated in progression of classical Wilms
tumor (WT) into the anaplastic variant (AWT), drug resistance, and poor
prognosis. Because of prognostic similarities, clear cell sarcoma of the
kidney (CCSK) has been classified with AWT and other aggressive
pediatric renal tumors, apart from congenital mesoblastic nephroma
(CMN), which is instead a relatively benign tumor of neonates.
Initially, CCSK and CMN were assumed to be ontologically related, but
the role of p53 in the pathogenesis of either disease has not been
sufficiently evaluated as in AWT. We examined the status of p53 in CMN
and CCSK in comparison to AWT by immunohistochemistry and mRNA analysis
of p53, the downstream effector p21(WAF-1/CIP-1) ( p21), the multidrug
resistance gene MDR-1, a putative target of p53, and the p53-antagonist
Mdm-2. Surprisingly, strong p53 nuclear immunoreactivity was found in
cultures from two CMN specimens, but not in frozen or fixed tumor tissue
from five other CMN specimens, nor in cell lines or tumor tissue from
CCSK. Sequence analysis excluded p53 mutations. The size of the p53 mRNA
in CMN and CCSK primary tumors excluded gross deletions or
rearrangements. Low levels of Mdm-2 mRNA in CCSK and CMN primary tumors
and cultures did not support a role for Mdm-2. Absence of MDR-1 mRNA
excluded MDR-1 in the drug-resistant phenotype of CCSK.
Cisplatin-induced p21 transactivation assays and G(1) cell cycle arrest
analyses showed that p21 transactivation and G(1) arrest occurred in
both CCSK and CMN cultures, demonstrating integrity of the p53 signal
transduction pathway. Absence of p53 functional abnormalities excluded
relationships between CCSK and CMN as in AWT, supporting the association
of cellular CMN with congenital fibrosarcomas as more recently proposed.
11
UI - 12124351
AU - Bates DO; Cui TG; Doughty JM; Winkler M; Sugiono M; Shields JD; Peat D;
TI -
Gillatt D; Harper SJ
VEGF165b, an inhibitory splice variant of vascular endothelial growth
factor, is down-regulated in renal cell carcinoma.
SO - Cancer Res 2002 Jul 15;62(14):4123-31
AD - Microvascular Research Laboratories, Department of Physiology,
Preclinical Veterinary School, University of Bristol, Bristol BS2 8EJ,
United Kingdom.
Angiogenesis is essential for tumor growth. Vascular endothelial growth
factor (VEGF) is the most potent growth factor of tumor neovasculature,
has been shown to be up-regulated in every tumor studied thus far, and
is correlated with tumor stage and progression. To determine whether
specific VEGF splice variants were differentially expressed in renal
cell carcinomas, 18 polar tumor samples were analyzed by reverse
transcription-PCR using primers designed to differentiate between VEGF
splice variants. Control tissue was derived from the opposite normal
pole. An amplicon of length consistent with the previously described
variant VEGF(148) was found in normal kidney tissue. Subsequent
sequencing revealed a new VEGF isoform formed by differential splicing
from the end of exon 7 into the 3' untranslated region of the mRNA.
Cloning of this transcript showed that translation would result in a
165-amino acid peptide with an alternative terminal 6 amino acids,
followed by a stop codon. We have termed this new isoform VEGF165b. This
isoform was present in 17 of 18 normal kidney samples but only 4 of 18
cases from matched malignant tissue. VEGF165b was therefore expressed in
a significantly higher proportion of normal tissue than malignant tissue
from the same patients (P < 0.001). To determine the functional
significance of this new isoform, we expressed the full-length protein
in a heterologous expression system. Conditioned medium containing this
isoform significantly and dose dependently inhibited VEGF165-mediated
proliferation, migration of endothelial cells, and vasodilatation of
mesenteric arteries. This novel isoform VEGF165b is therefore an
endogenous inhibitory form of VEGF that is down-regulated in renal
tumors and, therefore, may be anti-angiogenesis.
12
UI - 9662341
AU - Chevillard S; Radicella JP; Levalois C; Lebeau J; Poupon MF; Oudard S;
TI -
Dutrillaux B; Boiteux S
Mutations in OGG1, a gene involved in the repair of oxidative DNA
damage, are found in human lung and kidney tumours.
SO - Oncogene 1998 Jun 11;16(23):3083-6
AD - Departement de Radiobiologie et Radiopathologie, UMR217 CNRS-CEA
Radiobiologie Moleculaire et Cellulaire, Fontenay aux Roses, France.
The human OGG1 gene encodes a DNA glycosylase activity catalysing the
excision of the mutagenic lesion 7,8-dihydro-8-oxoguanine from
oxidatively damaged DNA. The OGG1 gene was localized to chromosome 3p25,
a region showing frequent loss of heterozygosity (LOH) in lung and
kidney tumours. In this study, we have analysed by RT-PCR the expression
of OGG1 in 25 small cell lung cancers, in 15 kidney carcinomas and the
15 normal kidney counterparts. The results show that OGG1 messenger RNA
can be detected in all tumours tested and that no significant difference
was observed in the level of expression between normal and tumoral
kidney tissues. Denaturing gradient gel electrophoresis (DGGE) was used
to screen this series of human tumours for alterations in the OGG1 cDNA.
The study revealed homozygous mutations in three tumours, two from lung
and one from kidney. Sequencing analysis of the mutants identified a
single base substitution in each of the three cases: two transversions
(GC to TA and TA to AT) and one transition (GC to AT). All three
substitutions cause an amino acid change in the hOgg1 protein. For the
mutant kidney tumour, the normal tissue counterpart shows a wild-type
profile. These results suggest a role for OGG1 mutations in the course
of the multistage process of carcinogenesis in lung or kidney.
13
UI - 10987279
AU - Audebert M; Chevillard S; Levalois C; Gyapay G; Vieillefond A;
TI -
Klijanienko J; Vielh P; El Naggar AK; Oudard S; Boiteux S; Radicella JP
Alterations of the DNA repair gene OGG1 in human clear cell carcinomas
of the kidney.
SO - Cancer Res 2000 Sep 1;60(17):4740-4
AD - Commissariat a l'Energie Atomique, Departement de Radiobiologie et
Radiopathologie, Fontenay aux Roses, France.
The OGG1 gene, which codes for a DNA repair protein with antimutator
activity, is located on chromosome 3p25, a frequent site of allelic
deletions in many types of human tumors, including renal clear cell
cancers. We present the analysis of 99 renal tumors for alterations in
the OGG1 gene to determine its association with tumorigenesis. Loss of
heterozygosity in the 3p25 region was found for 85% of the informative
cases. We detected somatic missense mutations of the OGG1 gene in 4 of
the 99 tumor samples. Biochemical analysis of the mutant proteins
revealed that a substitution at codon 46 impairs the enzymatic activity.
We also describe the occurrence of several polymorphisms as well as
aberrantly spliced OGG1 transcripts.
14
UI - 11765004
AU - Audebert M; Levalois C; Chevillard S; Dizdaroglu M; Boiteux S; Radicella
TI -
JP
hOGG1 gene alterations in human clear cell carcinomas of the kidney:
effect of single mutations in hOGG1 gene on substrate specificity of the
hOGG1 protein.
SO - Adv Exp Med Biol 2001;500():617-20
AD - CEA, UMR 217 CEA/CNRS, Departement de Radiobiologie et Radiopathologie,
Fontenay-aux-Roses, France.
15
UI - 12133548
AU - Zhang Q; Chen L; Liang L; Xi Z; Ding Y; Tong M; Zhang Z; Lee C; Guo Y
TI -
Renal cell carcinoma related novel gene, GYLZ-RCC18: cloning and
functional studies.
SO - Chin Med J (Engl) 2002 May;115(5):746-9
AD - Department of Urology and Institute of Urology, The First Affiliated
Hospital, Peking University, Beijing 100034, China.
zhanqian@public3.bta.com
OBJECTIVE: To clone the full length of renal cell carcinoma (RCC)
related novel gene GYLZ-RCC18 and study its function. METHODS: SMART
RACE technology was used to clone the full length of GYLZ-RCC18. RT-PCR
was used to detect its expression in renal cell carcinoma tissue at
different stages and grades. We transfected the antisense
oligonucleotide of GYLZ-RCC18 to renal cell carcinoma cell line, GRC-1,
and analyzed proliferation activity, growth rate, apoptosis, and
mortality changes. RESULTS: The full length of GYLZ-RCC18 (GenBank
accession number: BE825133) cDNA was about 3.5 kb. GYLZ-RCC18 had a
higher expression in higher grades and stages of renal cell carcinoma
than in lower ones. The expression of GYLZ-RCC18 in renal cell carcinoma
was much higher than in normal kidney. After the transfection of
GYLZ-RCC18 antisense oligonucleotide, the mortality of GRC-1 increased
significantly, while proliferative activity and growth rate were
substantially inhibited at the same time. The antisense oligonucleotide
induced apoptosis of GRC-1 through the entire observation time.
CONCLUSION: GYLZ-RCC18 is an important novel gene related to renal cell
carcinoma. Overexpression of this gene results in higher growth and
proliferative activity and has an antiapoptosis effect on renal cell
carcinoma cells. Transfection of the antisense oligonucleotide may
inhibit the generation and development of renal cell carcinoma.
16
UI - 12070600
AU - Henke RP; Erbersdobler A
TI -
Numerical chromosomal aberrations in papillary renal cortical tumors:
relationship with histopathologic features.
SO - Virchows Arch 2002 Jun;440(6):604-9
AD - Institute of Pathology, Taubenstrasse 28, 26122 Oldenburg, Germany.
Previous studies have indicated that a combined trisomy of chromosomes 7
and 17 is a constant finding in papillary renal cortical adenomas and
that papillary renal cell carcinomas are marked by additional trisomies
such as trisomy 12, 16, and 20. The aim of our study was to compare this
cytogenetic classification of papillary renal cortical tumors with
conventional histopathologic classification. We performed interphase
cytogenetics with enumeration probes for chromosomes 7, 12, 16, 17, and
20 on 41 papillary tumors found in 21 nephrectomy and 10 autopsy
kidneys. A total of 38 tumors harbored gains of chromosomes 7 or 17, and
most of these showed a trisomic signal distribution. The three tumors
with normal copy numbers for chromosomes 7 and 17 were a papillary
grade-2 carcinoma, a small adenoma (both with distinctive oxyphilic
cytoplasm), and a papillary carcinoma with focally clear cells. Gains
for chromosomes 12, 16, or 20 were found in 21 tumors and were
significantly associated with the presence of histologic criteria of
malignancy ( P<0.0001). Histopathologic and cytogenetic features of
malignancy were found in eight tumors smaller than 10 mm. There is a
good agreement of cytogenetic and histopathologic criteria of malignancy
in papillary renal cell tumors. Interphase cytogenetics might give
useful additional information in cases of doubt or when only small
biopsy specimens are available.
17
UI - 12131287
AU - Ghavamian R; Cheville JC; Lohse CM; Weaver AL; Zincke H; Blute ML
TI -
Renal cell carcinoma in the solitary kidney: an analysis of
complications and outcome after nephron sparing surgery.
SO - J Urol 2002 Aug;168(2):454-9
AD - Department of Laboratory Medicine, Health Sciences Research and Urology,
Mayo Clinic, Rochester, Minnesota, USA.
PURPOSE: We evaluated surgical techniques, pathological features and
extended outcomes in patients with renal cell carcinoma in a solitary
kidney treated with surgical excision. MATERIALS AND METHODS: Between
1970 and 1998, 76 patients underwent nephron sparing surgery for
sporadic renal cell carcinoma in a solitary kidney, including 63 with
tissue specimens available for pathological review who comprised the
cohort. Six (9.5%) patients had a congenitally absent kidney and 57
(90.5%) had previously undergone contralateral nephrectomy for renal
cell carcinoma. The clinical and pathological features examined were
patient age at nephron sparing surgery, sex, type of nephron sparing
surgery (enucleation, partial nephrectomy or ex vivo resection), tumor
size, nuclear grade, histological subtype and 1997 tumor stage. Overall
cancer specific, local recurrence-free and metastasis-free survival as
well as early (within 30 days of nephron sparing surgery) and late (30
days to 1 year after nephron sparing surgery) complications were
assessed. Univariate and multivariate analyses were done to test for the
associations of clinical and pathological features with outcome.
RESULTS: Most patients were treated with enucleation (36.5%), standard
partial nephrectomy (38.1%) or the 2 procedures (11.1%) and in 8 (12.7%)
ex vivo tumor resection was done. The renal cell carcinoma histological
subtypes were clear cell in 82.5% of cases, papillary in 15.9% and
chromophobe in 1.6%. Grade was 1 to 3 in 10 (15.9%), 42 (66.7%) and 10
(15.9%) tumors, respectively. At 5 and 10 years the overall survival
rate was 74.7% and 45.8%, the cancer specific survival rate was 80.7%
and 63.7%, the local recurrence-free survival rate was 89.2% and 80.3%,
and the metastasis-free survival rate was 69% and 50.4%, respectively.
Tumor stage and nuclear grade were significantly associated with death
from any cause, death from renal cell carcinoma and distant metastases
on multivariate analysis. Notably no patient with papillary or
chromophobe renal cell carcinoma died of renal cell carcinoma, or had
recurrence or metastasis. The type of nephron sparing surgery was not
significantly associated with outcome, although there were too few
patients with recurrence to assess the association of the type of
nephron sparing surgery with local recurrence. The most common early
complication was acute renal failure in 12.7% of cases, while the most
common late complications were proteinuria in 15.9% and renal
insufficiency in 12.7%. CONCLUSIONS: The 1997 tumor stage and nuclear
grade were significant predictors of death from any cause, death from
renal cell carcinoma and distant metastases in patients treated with
nephron sparing surgery for renal cell carcinoma involving a solitary
kidney. Nephron sparing surgery in a solitary kidney can be performed
safely and with minimal morbidity.
18
UI - 12131288
AU - Richter EN; Oevermann K; Buentig N; Storkel S; Dallmann I; Atzpodien J
TI -
Primary apoptosis as a prognostic index for the classification of
metastatic renal cell carcinoma.
SO - J Urol 2002 Aug;168(2):460-4
AD - Hamatologie und Onkologie and Urologische Klinik, Medizinische
Hochschule Hannover, Hannover, Germany.
PURPOSE: We identified novel biological markers of prognosis in primary
histopathological specimens from patients with metastatic renal cell
carcinoma. MATERIALS AND METHODS: Apoptotic indexes (terminal
deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick
end-labeling), proliferation rates (Ki-67 antigen), p21 (WAF1/cip1)
expression and CD95 (APO-1/Fas) expression were determined in paraffin
embedded nephrectomy specimens from 73 patients with histologically
confirmed, progressive metastatic disease. Kaplan-Meier survival
analysis, log rank statistics and 2-proportional Cox regression analysis
were done to identify new risk factors in addition to conventional
classification criteria, and demonstrate statistical independence.
RESULTS: Multivariate analysis indicated that primary tumor apoptosis (p
= 0.0116) and the interval from diagnosis to metastatic disease (p =
0.002) had a high predictive impact on overall survival after initial
diagnosis. Patients were assigned to 2 risk groups, namely a poor
prognosis group with a median survival of 20 months, defined by
apoptosis less than 6% in the primary tumor nephrectomy specimen and a
time from initial diagnosis to metastatic disease of less than 6 months,
and a good prognosis group with a median survival of 56 months, defined
as the absence of 1 or 2 risk factors. CONCLUSIONS: Our findings showed
that primary tumor apoptosis is a novel independent predictor in
patients with metastatic renal cell carcinoma at initial diagnosis. It
leads to a new prognostic index in the pretreatment classification of
metastatic renal cell carcinoma.
19
UI - 12131338
AU - Ogan K; Cadeddu JA
TI -
Re: Percutaneous radio frequency ablation of small renal tumors: initial
results.
SO - J Urol 2002 Aug;168(2):660; discussion 660-1
20
UI - 12131365
AU - Horiguchi A; Oya M; Shimada T; Uchida A; Marumo K; Murai M
TI -
Activation of signal transducer and activator of transcription 3 in
renal cell carcinoma: a study of incidence and its association with
pathological features and clinical outcome.
SO - J Urol 2002 Aug;168(2):762-5
AD - Department of Clinical Research and Urology, Saitama National Hospital
and Department of Pathology, Saitama Medical School, Saitama, Japan.
PURPOSE: Signal transducer and activator of transcription 3 (STAT3) is
known to have an important role in cytokine and growth factor signaling
pathways. In various types of human malignant tumors STAT3 has been
shown to be constitutively activated due to aberrant production of
cytokines and growth factors. We examined the presence of STAT3
activation and its association with pathological features and clinical
outcome in renal cell carcinoma cases. MATERIALS AND METHODS: We
examined 48 paraffin embedded renal cell carcinoma specimens and
corresponding nonneoplastic kidney tissues for the activation status of
STAT3 on immunohistochemistry using anti-phospho-specific (p)-STAT3
antibody, which recognizes only activated STAT3. Based on the percent of
cells with positive nuclear staining the activation status of STAT3 was
determined and categorized into 2 groups, including low-less than 10%
and high-90% or more tumor cells positive. The associations of the
activation status of STAT3 with pathological features and clinical
outcome were analyzed. RESULTS: Of 48 tumors 24 (50%) demonstrated high
levels of nuclear immunostaining for p-STAT3, while the other 24 (50%)
showed low levels. Adjacent nonneoplastic kidney tissues showed only
little immunostaining for p-STAT3. A significant association of high
levels of p-STAT3 with metastasis was observed (p = 0.0094). No
significant associations of p-STAT3 immunostaining with pathological
stage or grade were observed. A high level of p-STAT3 was a significant
indicator of a poor prognosis on univariate and multivariate analysis (p
= 0.0117 and 0.0439, respectively) CONCLUSIONS: Our results indicate a
high frequency of STAT3 activation in renal cell carcinoma, especially
in metastatic disease. STAT3 activation was an independent prognostic
variable in renal cell carcinoma cases. Our results strongly suggest
that the activation of STAT3 contributes to the development and
progression of renal cell carcinoma.
21
UI - 11993086
AU - Janetschek G; al-Zachrani H; Vrabec G; Leeb K
TI -
[Laparoscopic tumor nephrectomy]
SO - Urologe A 2002 Mar;41(2):101-6
AD - Abteilung fur Urologie, Krankenhaus der Elisabethinen, Fadingerstrasse
1, 4020 Linz/Osterreich. guenter.janetschek@elisabethinen.or.at
Initially, laparoscopic surgery in urology was restricted to the
treatment of benign diseases, whereas its role in the management of
malignant disease was restricted to purely diagnostic procedures. Only
recently has laparoscopy been introduced for the treatment of low stage
renal cell carcinoma (RCC), and the data on both surgical efficiency and
oncologic efficacy are very promising. Therefore, we present our
experience with laparoscopic radical nephrectomy and data from
literature. The technique of the transperitoneal approach is described
in detail. Retroperitoneoscopy is a good alternative, however. Intact
removal of the specimen within an organ bag to avoid tumor spillage is
an important detail of our technique. Our experience amounts to radical
nephrectomy in 121 patients. The indication was clinical stage T1-T2.
Mean operative time and blood loss was 2.4 h and 154 ml, respectively.
The rate of minor or major complications was 5% and 4%, respectively.
There was no conversion to open surgery in any patient. Mean
postoperative hospital stay was 6.1 days. Data on tumor control are
available for 73 patients with a mean follow-up of 13.3 months. There
was no recurrence within this period. Radical nephrectomy for low-stage
RCC is associated with low morbidity and great surgical efficiency. The
rates for local recurrences and metastases are low, tumor-specific
survival is high. However, there is still a lack of long-term data on
large series of patients. Despite this fact, laparoscopy is already
widely accepted for this indication, and it is quite likely that it will
become the standard treatment.
22
UI - 11877969
AU - Pereverzev AS; Shtsukin DV; Iliukhin IuA
TI -
[Long-term results of organ-preserving surgeries for renal cell
carcinoma]
SO - Urologiia 2002 Jan-Feb;(1):28-31
The paper presents long-term results of conservative surgical treatment
of 148 patients with renal cell carcinoma (RCC). Cancer-specific
survival, local recurrence and distant metastases rates were estimated.
Overall cancer-specific survival reached 91.8%. For patients with
imperative indications this survival was 79.6%, for elective
patients--98%. Recurrent RCC was observed in 10(6.8%) patients:
imperative group--8(5.4%), elective group--2(1.3%). Distant metastases
were detected in 7(4.7%) patients. The elective group had no metastases.
General level of multifocality of sporadic renal cancer was 6.7%, for
tumors < 4 cm--1.2%. The basic criterion of the decision on organ-saving
operation is tumor size under 4 cm. The size of the primary tumor
determines the level of local recurrences and distant metastases. To
select the optimal group of patients, genetic markers of tumor
multifocality should be identified.
23
UI - 12165445
AU - Watanabe N; Kobayashi H; Hirama T; Kikuta A; Koizumi S; Tsuru T; Kaneko
TI -
Y
Cryptic t(12;15)(p13;q26) producing the ETV6-NTRK3 fusion gene and no
loss of IGF2 imprinting in congenital mesoblastic nephroma with trisomy
11: fluorescence in situ hybridization and IGF2 allelic expression
analysis.
SO - Cancer Genet Cytogenet 2002 Jul 1;136(1):10-6
AD - Departments of Cancer Chemotherapy and Medicine, Saitama Cancer Center
Hospital, Ina, Saitama 362-0806, Japan.
In the present fluorescence in situ hybridization (FISH) study of six
congenital mesoblastic nephromas (CMNs) using ETV6 and NTRK3 probes as
well as a chromosome 15 painting probe, we identified a cryptic
reciprocal translocation, t(12;15)(p13;q26), in one tumor, and an
insertion, ins(12;15)(p13;q22q26), in another that were not previously
identified by cytogenetic analysis. An interphase FISH study with the
same probes detected the ETV6-NTRK3 fusion signal in all three cellular
or mixed type tumors, but not in all three classical type tumors.
Reverse transcriptase polymerase chain reaction (RT-PCR) analysis
detected the ETV6-NTRK3 fusion transcript in the three cellular or mixed
type tumors, but not in the three classical type tumors. FISH analysis
using a chromosome 11-centromere probe detected trisomy or tetrasomy 11
in all three tumors with the ETV6-NTRK3 fusion signal. To clarify
whether IGF2, a paternally expressed gene on chromosome 11, has a
certain role in the tumorigenic process of CMN through a loss of
imprinting (LOI), we studied IGF2 allelic expression. We found no LOI in
two cellular or mixed type tumors or in two classical type tumors, and
concluded that the role of the LOI of IGF2 is not essential for the
development and progression of CMN with or without trisomy 11.
Furthermore, we showed no rearrangements of the MLL gene, which is
frequently rearranged in acute leukemia with +11 in the three CMN tumors
with +11.
24
UI - 12165447
AU - Nagao K; Yoshihiro S; Matsuyama H; Yamaguchi S; Oba K; Naito K
TI -
Clinical significance of allelic loss of chromosome region 5q22.3
approximately q23.2 in nonpapillary renal cell carcinoma.
SO - Cancer Genet Cytogenet 2002 Jul 1;136(1):23-30
AD - Department of Urology, Yamaguchi University School of Medicine, 1-1-1,
Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
katsumai@po.cc.yamaguchi-u.ac.jp
To analyze the clinical significance of copy number gain and loss at
chromosome region 5q21 approximately q23, 105 nonpapillary renal cell
carcinomas (RCC) were examined by interphase cytogenetic analysis using
the dual-color fluorescence in situ hybridization (FISH) technique. DNA
probes for D5S23 (5p15.2), cCI5-243 (5q21.2 approximately q21.3), and
cCI5-215 (5q22.3 approximately q23.2) were used, and the signals for
cCI5-243 and cCI5-215 were compared with those for D5S23 as the
numerical control. Aneusomy (three or more copies) of chromosome 5 was
found in 22 tumors (21.0%). Aneusomy was significantly correlated with
loss at 5q21 approximately q23, while disomy with gain at 5q21
approximately q23 (P<0.05). Aneusomy was also significantly related to
poor disease-specific survival (P<0.01). Gain and loss at cCI5-243 were
seen in 34 (32.4%) and 59 (56.2%) tumors, respectively, while gain and
loss at cCI5-215 occurred in 55 (52.4%) and 45 (42.9%) cases,
respectively. The frequency of gain at cCI5-215 was significantly
correlated with a smaller tumor diameter (7 cm or less, P<0.05), while
loss with a larger one (>7 cm, P<0.05). Both loss at cCI5-215 and
aneusomy of chromosome 5 were significantly related to poor
disease-specific survival (P<0.05). In conclusion, alterations of
chromosome 5 (including allelic loss of 5q22.3 approximately q23.2)
could be a useful genetic marker for predicting the patient prognosis of
RCC.
25
UI - 11999462
AU - Salvador-Bayarri J; Rodriguez-Villamil L; Imperatore V; Palou Redorta J;
TI -
Villavicencio-Mavrich H; Vicente-Rodriguez J
Bladder neoplasms after nephroureterectomy: does the surgery of the
lower ureter, transurethral resection or open surgery, influence the
evolution?
SO - Eur Urol 2002 Jan;41(1):30-3
AD - Departament of Urology, Fundacio Puigvert, Barcelona, Spain.
urologia@fundacio-puigvert.es
OBJECTIVE: Nephroureterectomy is the treatment of choice for tumors of
the upper urinary tract (UUTT). In 1952, a modified version of this
technique was described, involving endoscopic detachment of the ureter
followed by nephroureterectomy with a single lumbar incision. We
reviewed a retrospective survey to assess whether UUTT patients treated
with nephroureterectomy with no prior history of bladder tumor had
different rates of incidence or different sites of bladder recurrence
according to the specific technique employed. METHODS: Patients were
divided into group A, 87 patients who underwent a double incision
nephroureterectomy and group B with 58 patients with prior detachment of
the ureter. In both groups, incidence was calculated for two variables
(bladder tumor recurrences and homolaterality of such recurrences) and
chi-square tested. Results: Bladder tumor was diagnosed at follow-up in
39% of patients in group A and 34.5% in group B, with no statistically
significant difference (N.S.). Bladder tumor recurrences were
homolateral to UUTT in 50% of group A cases and 55% of group B cases
(N.S.). CONCLUSIONS: Although this is a retrospective survey of two
asynchronous groups, given the similar nature of the UUTT cases in both
groups and the fact that no statistically significant differences have
been found, it is reasonable to conclude that nephroureterectomy with
prior endoscopic detachment of the ureter is a safe and radical
procedure.
26
UI - 11912179
AU - Bodmer D; Eleveld M; Kater-Baats E; Janssen I; Janssen B; Weterman M;
TI -
Schoenmakers E; Nickerson M; Linehan M; Zbar B; van Kessel AG
Disruption of a novel MFS transporter gene, DIRC2, by a familial renal
cell carcinoma-associated t(2;3)(q35;q21).
SO - Hum Mol Genet 2002 Mar 15;11(6):641-9
AD - Department of Human Genetics, University Medical Center Nijmegen,
Nijmegen, The Netherlands. d.bodmer@antrg.azn.nl
Previously, we described a family with a significantly increased
predisposition for renal cell cancer co-segregating with a
t(2;3)(q35;q21) chromosomal translocation. Several primary tumors of the
clear cell type from different family members were analyzed at a
molecular level. Loss of the derivative chromosome 3 was consistently
found. In addition, different somatic Von Hippel Lindau (VHL) gene
mutations were observed in most of the tumors analyzed, even within the
same patient. Based on these results a multistep tumorigenesis model was
proposed in which (non-disjunctional) loss of the derivative chromosome
3 represents an early event and somatic mutation of the VHL gene
represents a late event related to tumor progression. More recently,
however, we noted that these two anomalies were absent in at least one
early-stage tumor sample that we tested. Similar results were obtained
in another family with renal cell cancer and t(3;6)(q12;q15), thus
suggesting that another genetic event may precede these two oncogenetic
steps. We speculate that deregulation of a gene(s) located at or near
the translocation breakpoint may act as such. In order to identify such
genes, a detailed physical map encompassing the 3q21 breakpoint region
was constructed. Through a subsequent positional cloning effort we found
that this breakpoint targets a hitherto unidentified gene, designated
DIRC2 (disrupted in renal cancer 2). Computer predictions of the
putative DIRC2 protein showed significant homology to different members
of the major facilitator superfamily (MFS) of transporters. Based on
additional DIRC2 expression and mutation analyses, we propose that the
observed gene disruption may result in haplo-insufficiency and, through
this mechanism, in the onset of tumor growth.
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