Información sobre riesgo, prevención, detección, síntomas, diagnosis, tratamiento y apoyo para el cáncer.
Información sobre el tratamiento del cáncer incluyendo quirúrgica, quimioterapia, radioterapia, estudios clínicos, terapia con protón, medicina complementaria avanzadas.
OncoLink se complace en ofrecer una amplia lista de lista completa de los agentes quimioterapéuticos más comúnmente usados??. Esta guía de referencia incluye información sobre la forma en que cada fármaco se administra, cómo funcionan, y los pacientes los efectos secundarios comunes pueden experimentar.
Maneras que los pacientes de cáncer y las personas que le cuidan puedan enfrentar el cáncer, los efectos secundarios, nutrición, cuestiones en general sobre el apoyo para el cáncer, duelo/decisiones sobre el termino de vida, y experiencias compartidas por sobrevivientes.
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Ultima Vez Modificado: 1 de mayo del 2002
UI - 11898515
AU - Gropman AL
TI - Diagnosis and treatment of childhood mitochondrial diseases.
SO - Curr Neurol Neurosci Rep 2001 Mar;1(2):185-94
AD - National Human Genome Research Institute, Neurogenetics Branch, National Institutes of Neurologic Disorders and Stroke, National Institutes of Health, 10 Center Drive, Building 10, Room 3B04, Bethesda, MD 20892, USA. firstname.lastname@example.org
Mitochondrial cytopathies are caused by genetic alterations of nuclear- or mitochondrial-encoded genes involved in the synthesis of subunits of the electron transport chain. Mutations of mitochondrial DNA are associated with a wide range of clinical presentations [1-4]. The ubiquitous nature of mitochondria and the role of the mitochondria in cellular metabolism result in the potential for any tissue in the body to be affected [5-7,8..,9]. Although some children with mitochondrial disease present with life-threatening lactic acidosis in the newborn period, the majority of children come to clinical attention for nonspecific problems, including failure to thrive, developmental delay, seizures, hypotonia, and loss of developmental milestones. The diagnosis of these disorders is made through careful clinical evaluation, coupled with biochemical, morphologic, and molecular biologic techniques. Genetic counseling is difficult due to unique aspects of mitochondrial genetics. Despite advances in our understanding of mitochondrial biochemistry and genetics, treatment options remain limited.
UI - 11778984
AU - Burke W; Pinsky LE; Press NA
TI - Categorizing genetic tests to identify their ethical, legal, and social implications.
SO - Am J Med Genet 2001 Fall;106(3):233-40
AD - Department of Medical History and Ethics, University of Washington, Seattle 98195, USA. email@example.com
Practice standards in medical genetics provide an implicit guide to the ethical, legal, and social implications (ELSI) of genetic tests. The common use of nondirective counseling reflects the principle that many testing decisions should be determined by personal values. Yet geneticists make test recommendations in some circumstances, e.g., RET mutation testing for MEN2 and newborn screening for phenylketonuria (PKU). Conversely, many geneticists recommend against testing for Apolipoprotein E (ApoE) alleles to predict Alzheimer disease (AD) risk. Taken together, these examples suggest that genetic tests can be categorized by a joint consideration of clinical validity and availability of effective treatment for persons who test positive. For genetic tests with high clinical validity/no treatment (e.g., presymptomatic testing for Huntington disease), the predominant concern is adequate nondirective counseling to ensure an informed, autonomous decision. By contrast, the predominant concern for tests with high clinical validity/effective treatment (e.g., PKU) is assuring access to care for eligible persons. For tests with limited clinical validity/no treatment (e.g., ApoE), recommending against test use can be justified on the principle of avoiding harm. For a fourth category, tests with limited clinical validity/effective treatment (e.g., HFE mutation testing for hereditary hemochromatosis), net benefit is the issue: the balance between potential benefits of treatment and potential harms of genetic labeling must be weighed. Where uncertainty exists concerning both clinical validity and effectiveness of treatment, as in the case of BRCA 1/2 mutation testing, the value of testing may vary according to different testing contexts. This approach to test categorization allows a rapid determination of the predominant ELSI concerns for different kinds of genetic tests and identifies the data most urgently needed for test evaluation.
UI - 11955446
AU - Kramps T; Peter O; Brunner E; Nellen D; Froesch B; Chatterjee S; Murone
TI - M; Zullig S; Basler K Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex.
SO - Cell 2002 Apr 5;109(1):47-60
AD - Institut fur Molekularbiologie, Universitat Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
Wnt/Wingless signaling controls many fundamental processes during animal development. Wnt transduction is mediated by the association of beta-catenin with nuclear TCF DNA binding factors. Here we report the identification of two segment polarity genes in Drosophila, legless (lgs), and pygopus (pygo), and we show that their products are required for Wnt signal transduction at the level of nuclear beta-catenin. Lgs encodes the homolog of human BCL9, and we provide genetic and molecular evidence that these proteins exert their function by physically linking Pygo to beta-catenin. Our results suggest that the recruitment of Pygo permits beta-catenin to transcriptionally activate Wnt target genes and raise the possibility that a deregulation of these events may play a causal role in the development of B cell malignancies.
UI - 11760823
AU - Struse HM; Montoya ID
TI - Health services implications of DNA testing.
SO - Clin Lab Sci 2001 Fall;14(4):247-51
AD - Affiliated Systems Corporation, Houston TX 77027-6022, USA.
This review article summarizes the state of the art in genetic testing and discusses the many issues that new technologies have raised. A health services perspective is offered to aid in providing laboratorians with an understanding of the dilemma that society faces with the exponential advances in knowledge. Unmistakably, these new technologies are a mixed blessing: on the one hand, diagnoses can be made with greater accuracy and preventive measures implemented more fruitfully and individuals may be more conclusively identified and/or exonerated for forensic purposes. On the other hand, however, are the very real concerns that discrimination under a medical guise will be encouraged and that privacy rights may be compromised. Another important issue is how the laboratory profession will serve in moving these new technologies from research to practice. We examine the role of the CLS in moving forward to a role of patient counselor and advocate in the emerging complex world of DNA-related biotechnology.
UI - 11873549
AU - Fries MH; Holt C; Carpenter I; Carter CL; Daniels J; Flanagan J; Murphy
TI - K; Hailey BJ; Martin L; Hume R; Hudson G; Cadman M; Weatherly R; Nunes ME Guidelines for evaluation of patients at risk for inherited breast and ovarian cancer: recommendations of the Department of Defense Familial Breast/Ovarian Cancer Research Project.
SO - Mil Med 2002 Feb;167(2):93-8
AD - Air Force Medical Genetics Center, Keesler Air Force Base, MS 39534, USA.
Patients at high risk for inherited breast and/or ovarian cancer are frequently encountered in all medical specialties. Department of Defense, Health Affairs funding as part of the Breast Cancer Education and Awareness Program was used to develop a comprehensive program for the identification, counseling, genetic testing, and long-term follow-up of such high-risk patients. This article reports the recommendations for high-risk patient management based on 4 years of evaluation and care, including discussions of the approach to counseling, indications for genetic testing, post-testing counseling, patient surveillance with examination, imagining, and laboratory testing, and suggested options for surgical and chemoprophylaxis as well as lifestyle modifications.
UI - 11873550
AU - Fries MH; Holt C; Carpenter I; Carter CL; Daniels J; Flanagan J; Murphy
TI - K; Hailey BJ; Martin L; Hume R; Hudson G; Cadman M; Weatherly R; Nunes ME Diagnostic criteria for testing for BRCA1 and BRCA2: the experience of the Department of Defense Familial Breast/Ovarian Cancer Research Project.
SO - Mil Med 2002 Feb;167(2):99-103
AD - Air Force Medical Genetics Center, Keesler Air Force Base, MS 39534, USA.
The Department of Defense Familial Breast/Ovarian Cancer Research Project has offered genetic counseling and testing for BRCA1 and BRCA2 on a research basis to patients meeting specific diagnostic criteria, with risk for BRCA1 and BRCA2 mutations calculated based on the Couch model. In 2.5 years, 250 patients were evaluated and 101 patients met criteria requirements, including 33 who met criteria in more than one category. Ninety patients elected to undergo DNA testing. In this group of 90 patients, 14 mutations (15.5%) and 16 unclassified variants (17.7%) were identified. The most common inclusion criteria were onset of breast/ovarian cancer before age 45 years (n = 32) and onset of breast/ovarian cancer before age 45 years with strong family history (n = 21). However, when number of mutations and unclassified variants found were compared separately across all diagnostic criteria (including those of more than one capacity) using the chi 2 statistic, no significant differences were seen among the categories to suggest that one criterion was more predictive of mutations or variants than another. Couch risk values for patients with mutations showed a mean of 14% and ranged from 3.2 to 43.5% (range for all patients, 1.2-69.7%). These findings emphasize the importance of using multiple diagnostic criteria and suggest that a Couch risk value of > 3% may be useful in selecting patients for testing. The data also underscore the necessity of genetic counseling in the testing process, particularly given the large number of unclassified variants diagnosed and their uncertain status for disease predisposition.
UI - 11912108
AU - Pickering-Brown SM; Richardson AM; Snowden JS; McDonagh AM; Burns A;
TI - Braude W; Baker M; Liu WK; Yen SH; Hardy J; Hutton M; Davies Y; Allsop D; Craufurd D; Neary D; Mann DM Inherited frontotemporal dementia in nine British families associated with intronic mutations in the tau gene.
SO - Brain 2002 Apr;125(Pt 4):732-51
AD - The School of Biological Sciences, Division of Neuroscience, University of Manchester, UK.
Genetic screening of 171 patients with frontotemporal lobar degeneration disclosed 14 patients, across nine pedigrees, with mutations in the intron to exon 10 in the tau gene, a region regulating the splicing of exon 10 via a stem loop mechanism. Thirteen of these patients had the +16 splice site mutation and one had the +13 splice site mutation. Affected members of all nine families presented with changes in behaviour and social conduct that were prototypical of frontotemporal dementia (FTD). In all patients with the +16 splice site mutation, the behavioural profile was characterized by disinhibition, restless overactivity, a fatuous affect, puerile behaviour and verbal and motor stereotypies. The single patient with the +13 mutation presented a contrasting picture of apathy and inertia. In addition, all patients had evidence of semantic loss. Pathologically, five of the six patients so far autopsied shared frontotemporal atrophy with involvement of the substantia nigra. The underlying histology was that of microvacuolar-type cortical degeneration with a few swollen cells. Tau pathology was widespread throughout the brain and present in neurones and glial cells, mostly in the frontal and temporal cortical regions. This was in the form of neurofibrillary tangles and amorphous tau deposits (pre-tangles); Pick bodies were not observed. Ultrastructurally, the tau filaments had a twisted, ribbon-like morphology distinct from the paired helical filaments of Alzheimer's disease. One patient died from an unrelated illness whilst in the early clinical stages of FTD. In this patient, cortical microvacuolar and astrocytic changes were absent, though there were scattered neurones and glial cells, immunoreactive to tau, throughout the cortical and subcortical regions. The disease process underlying the neurodegeneration within these inherited forms of FTD may therefore stem directly from early, primary alterations in the function of tau. All eight families with the +16 mutation seem to be part of a common extended pedigree, possibly originating from a founder member residing within the North Wales region of Great Britain.
UI - 11912113
AU - Caparros-Lefebvre D; Sergeant N; Lees A; Camuzat A; Daniel S; Lannuzel
TI - A; Brice A; Tolosa E; Delacourte A; Duyckaerts C Guadeloupean parkinsonism: a cluster of progressive supranuclear palsy-like tauopathy.
SO - Brain 2002 Apr;125(Pt 4):801-11
AD - Neurologie, Centre Hospitalier Universitaire de la Guadeloupe, Pointe a Pitre, French West Indies. firstname.lastname@example.org
An unusually high frequency of atypical Parkinson syndrome has been delineated over the last 5 years in the French West Indies. Postural instability with early falls, prominent frontal lobe dysfunction and pseudo-bulbar palsy were common and three-quarters of the patients were L-dopa unresponsive. One-third of all patients seen had probable progressive supranuclear palsy (PSP). This new focus of atypical parkinsonism is reminiscent of the one described in Guam and may be linked to exposure to tropical plants containing mitochondrial complex I inhibitors (quinolines, acetogenins, rotenoids). Two hundred and twenty consecutive patients with Parkinson's syndrome seen by the neurology service at Pointe a Pitre, Guadeloupe University Hospital were studied. Currently accepted operational clinical criteria for Parkinson's syndromes were applied. The pathological findings of three patients who came to autopsy are reported. Fifty-eight patients had probable PSP, 96 had undetermined parkinsonism and 50 had Parkinson's disease, 15 had amyotrophic lateral sclerosis with parkinsonism and one had probable multiple system atrophy. All three PSP patients in whom post-mortem study was performed had early postural instability, gaze palsy and parkinsonian symptoms, followed by a frontolimbic dementia and corticobulbar signs. Neuropathological examination showed an accumulation of tau proteins, predominating in the midbrain. There was an exceptionally large accumulation of neuropil threads in Case 1. Biochemical studies detected a major doublet of pathological tau at 64 and 69 kDa in brain tissue homogenates. All cases were homozygous for the H1 tau haplotype, but no mutation of the tau gene was observed. Clinical, neuropathological and biochemical features were compatible with the diagnosis of PSP, although some unusual pathological features were noted in Case 1. A cluster of cases presenting with atypical parkinsonism is reported. Guadeloupean parkinsonism may prove to be a tauopathy identical or closely related to PSP.
UI - 11927624
AU - Hogeveen KN; Cousin P; Pugeat M; Dewailly D; Soudan B; Hammond GL
TI - Human sex hormone-binding globulin variants associated with hyperandrogenism and ovarian dysfunction.
SO - J Clin Invest 2002 Apr;109(7):973-81
AD - Department of Obstetrics and Gynecology, University of Western Ontario, London, Ontario, Canada.
The access of testosterone and estradiol to target tissues is regulated by sex hormone-binding globulin (SHBG) in human blood. Serum SHBG levels are low in patients with hyperandrogenism, especially in association with polycystic ovarian syndrome (PCOS) and in individuals at risk for diabetes and heart disease. Here, we identify SHBG coding region variations from a compound heterozygous patient who presented with severe hyperandrogenism during pregnancy. Serum SHBG levels in this patient measured 2 years after her pregnancy were exceptionally low, and her non-protein-bound testosterone concentrations greatly exceeded the normal reference range. A single-nucleotide polymorphism within the proband's maternally derived SHBG allele encodes a missense mutation, P156L, which allows for normal steroid ligand binding but causes abnormal glycosylation and inefficient secretion of SHBG. This polymorphism was identified in four other patients with either PCOS, ioiopathic hirsutism, or ovarian failure. The proband's paternal SHBG allele carries a single-nucleotide deletion within exon 8, producing a reading-frame shift within the codon for E326 and a premature termination codon. CHO cells transfected with a SHBG cDNA carrying this mutation fail to secrete the predicted truncated form of SHBG. To our knowledge, these are the first examples of human SHBG variants linked to hyperandrogenism and ovarian dysfunction.
UI - 11988625
AU - Rundek T; Elkind MS; Pittman J; Boden-Albala B; Martin S; Humphries SE;
TI - Juo SH; Sacco RL Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes: the Northern Manhattan Prospective Cohort Study.
SO - Stroke 2002 May;33(5):1420-3
AD - Neurological Institute, New York Presbyterian Hospital, Columbia University, New York, NY 10032, USA. email@example.com
BACKGROUND AND PURPOSE: Atherosclerosis is a complex disorder with hereditary and environmental causes. Carotid artery intima-media wall thickness (IMT) is a useful measure of atherosclerosis. The objective of this study was to determine the association between carotid IMT and functional promoter variants of stromelysin-1 (MMP3: -1612 5A>6A), interleukin-6 (IL6: -174G>C), and hepatic lipase (HL: -480C>T) genes. METHODS: B-mode carotid ultrasound was performed among 87 subjects (mean age, 70+/-12 years; 55% women; 60% Caribbean-Hispanic, 25% black, and 13% white) from the Northern Manhattan Prospective Cohort Study. Carotid IMT was calculated as a composite measure (mean of the maximum IMT in the bifurcation, the common carotid artery, and the internal carotid artery). RESULTS: For all polymorphisms, genotype distribution was not significantly different from Hardy-Weinberg equilibrium. The frequencies of the rare alleles were as follows: MMP3 -1612 5A>6A, 0.31 (95% CI, 0.25 to 0.39); IL6 -174 G>C, 0.20 (95% CI, 0.13 to 0.25); and HL -480 C>T, 0.45 (95% CI, 0.35 to 0.50). Carotid IMT in the sample was 0.78+/-0.18 mm. Subjects with the MMP3 genotype 6A6A had 8% greater mean carotid IMT than the other MMP3 genotypes combined (0.95+/-0.17 versus 0.87+/-0.15 mm; P=0.04). Subjects with the IL6 genotype GG had 11% greater IMT (0.85+/-0.17 versus 0.76+/-0.16 mm; P=0.03), and those with the HL genotype CC had 13% greater IMT (0.87+/-20 versus 0.76+/-0.18 mm; P=0.02) than the other genotypes combined. Adjustment for other risk factors did not change these associations. CONCLUSIONS: Carotid IMT is higher among subjects homozygous for functional variants in genes related to matrix deposition (MMP3 -16126A), inflammation (IL6 -174G), and lipid metabolism (HL -480C). These associations were independent of race-ethnicity and some environmental exposures. Further studies are needed to confirm these genotype-phenotype associations.
UI - 11973868
AU - Nevanlinna H; Kallioniemi OP
TI - [Susceptibility genes of familiar breast cancer in Finland]
SO - Duodecim 1999;115(21):2365-74
AD - HYKS:n naistenklinikka, tutkimuslaboratorio PL 140, 00029 HYKS. firstname.lastname@example.org
UI - 11960582
AU - Pallares-Ruiz N; Blanchet P; Mondain M; Low-Hong S; Demaille J;
TI - Claustres M; Roux AF Evaluation of dHPLC for CX26 mutation screening in patients from southern France with sensorineural deafness.
SO - Genet Test 2001 Winter;5(4):339-43
AD - Laboratoire de Genetique Moleculaire, CHU Montpellier, France.
The GJB2 gene (or CX26 for connexin 26) is one of the major genes causing nonsyndromic sensorineural hearing loss (NSSNHL). More than 50 sequence variations have been identified as polymorphisms or associated with autosomal or recessive forms of deafness. Though a major mutation, 35delG, is easily detectable by PCR digest; it is often present in the compound heterozygous state in our population in trans with recurrent, but less frequent, mutations. The CX26 gene is composed of a single coding exon that facilitates sequencing strategies. However, for mutation screening purposes, it is necessary to use high-throughput and cost-effective genotyping methods. Therefore, we have assessed denaturing high-performance liquid chromatography (dHPLC) in patients with known mutations in the CX26 gene. We conclude that dHPLC analysis is suitable for rapid and reliable scanning of the gene in deaf patients.
UI - 11861307
AU - Hofmann WK; Jones LC; Lemp NA; de Vos S; Gschaidmeier H; Hoelzer D;
TI - Ottmann OG; Koeffler HP Ph(+) acute lymphoblastic leukemia resistant to the tyrosine kinase inhibitor STI571 has a unique BCR-ABL gene mutation.
SO - Blood 2002 Mar 1;99(5):1860-2
AD - Division of Hematology/Oncology, Cedars Sinai Research Institute, UCLA School of Medicine, Los Angeles, California 90048, USA. email@example.com
The tyrosine kinase inhibitor STI571 is a promising agent for the treatment of advanced Philadelphia chromosome positive (Ph(+)) acute lymphoblastic leukemia (ALL), but resistance develops rapidly in most patients after an initial response. To identify mechanisms of resistance to STI571, 30 complementary DNAs (including 9 matched samples) obtained from the bone marrow of individuals with Ph(+) ALL were analyzed by direct sequencing of a 714-base pair region of ABL encoding for the adenosine triphosphate (ATP)-binding site and the kinase activation loop. A single point mutation was found at nucleotide 1127 (GI6382056) resulting in Glu255Lys. This mutation occurred in 6 of 9 patients (67%) following their treatment with STI571 but not in the samples from patients before beginning treatment with STI571. Glu255Lys is within the motif important for forming the pocket of the ATP-binding site in ABL and it is highly conserved across species. In conclusion, Ph(+) ALL samples resistant to STI571 have a unique mutation Glu255Lys of BCR-ABL.
UI - 11963951
AU - Marchant GE
TI - Genetics and toxic torts.
SO - Seton Hall Law Rev 2001;31(4):949-82
AD - Center for the Study of Law, Science & Technology, Arizona State University College of Law, USA.
UI - 11977532
AU - Katai M; Sakurai A; Fukushima Y
TI - [Genetic testing and counseling for familial tumor syndromes]
SO - Gan To Kagaku Ryoho 2002 Apr;29(4):502-7
AD - Division of Molecular and Clinical Genetics, Shinshu University Hospital.
Recent developments in molecular biology have increased our understanding of the genetics of familial tumor syndromes. Isolation of the responsible genes has made it possible to identify gene carriers before they manifest clinical symptoms, which enables early detection of disease and at times prophylactic surgery. Indications for genetic testing of susceptible family members, however, should be carefully considered. Genetic counseling must be provided to clients before genetic tests. Patients should be provided with the latest knowledge on the disease and appropriately informed of the benefits and possible problems associated with genetic test, as such information is essential for clients to decide whether they will undergo such tests. Genetic medicine is not sufficiently available at present in Japan. Establishment of genetic services that deal with genetic counseling, family support and ethical, social and legal issues is strongly desired.
UI - 11977534
AU - Miyoshi Y; Noguchi S
TI - [Genetic test and prophylactic treatment in breast cancer families]
SO - Gan To Kagaku Ryoho 2002 Apr;29(4):512-22
AD - Dept. of Surgical Oncology, Osaka University Graduate School of Medicine.
Fifteen (13.3%) and 21 (18.6%) deleterious germline mutations were identified in BRCA1, and BRCA2 genes among 113 Japanese breast cancer families. We found a BRCA1 codon 63 (nucleotide 307) nonsense mutation and a 4-bp deletion at codon 1858 (nucleotide 5802) of BRCA2 in 4 and 7 independent families, respectively. Haplotype analysis has revealed that these two mutations were founder mutations. Lifetime risk of breast cancer in BRCA1 or BRCA2 mutation carriers was estimated at nearly 80%, and that of ovarian cancer in BRCA1 mutation carriers was about 40%. A questionnaire survey as to the genetic testing (BRCA1 and BRCA2) and prevention was carried out with 146 healthy women (hospital workers or medical students) and 84 breast cancer patients. About 80% of healthy women as well as breast cancer patients responded positively to the genetic testing, based on the assumption their's was a breast cancer family, and about 20% of each group answered that they would opt for prophylactic mastectomy and oophorectomy if they were found to be germline mutation carriers. These results indicate that genetic testing and prophylactic surgery would be acceptable among a considerable number of Japanese women, and seem to support the establishment an infrastructure for genetic testing in Japan.
UI - 11804383
AU - Pignata S; Ballatori E; Favalli G; Scambia G
TI - Quality of life: gynaecological cancers.
SO - Ann Oncol 2001;12 Suppl 3():S37-42
AD - Oncologia Medica B. Istituto Nazionale Tumori, Naples, Italy. firstname.lastname@example.org
The clinical management of gynaecological cancer patients has been mainly focused on prolonging the survival of the patients. Thus, research on MEDLINE using as keywords 'Quality of Life' (QoL) allowed us to identify few papers which reported data on QoL in gynecological oncology. However, the assessment of QoL is becoming one of the most important issues in gynecological oncology, and there is a growing interest in including quality of life measurements in clinical trials. In fact, in several randomised trials on ovarian cancer now ongoing in Europe, the evaluation of QoL has been planned. The one underlying this article focuses on the symptoms and problems particular to gynecologic cancer and the treatments of them that could affect quality of life evaluations. These include limitations of sexual activity and fertility, early menopause, chemotherapy induced toxicity, and loss of body image. In this report, we will discuss the aspects affecting the QoL in gynaecological cancer in relation to surgical treatment, medical therapy, and follow-up.
UI - 11891502
AU - Neumann HP; Hoegerle S; Manz T; Brenner K; Iliopoulos O
TI - How many pathways to pheochromocytoma?
SO - Semin Nephrol 2002 Mar;22(2):89-99
AD - Nephrology Section, Department of Medicine, Albert-Ludwigs University, Freiburg, Germany. email@example.com
Pheochromocytomas, like several other tumors, may be either sporadic or the manifestation of a familial cancer syndrome. Recently, major advances have occurred in both the understanding of diverse molecular mechanisms leading to pheochromocytoma and the diagnostic modalities available for detection of the disease. Familial pheochromocytoma may be a manifestation of multiple endocrine neoplasia type 2 (MEN-2), von Hippel-Lindau (VHL), or neurofibromatosis-1 (NF 1) disease. Tumor-suppressor genes responsible for the familial occurrence of extra-adrenal pheochromocytoma, called paraganglioma, have been identified. This wealth of genetic information, coupled with the availability of sensitive and specific biochemical tests as well as imaging studies, allows for genetic screening and early diagnosis of pheochromocytoma. In addition, genetic screening of relatives at risk is now feasible. In this article, we review recent clinical and molecular advances in our understanding of pheochromocytoma. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11708319
AU - Park WY
TI - [Application of DNA chip technology to biomedical research]
SO - Exp Mol Med 2001 Apr 21;33(1 Suppl):113-24
AD - Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Korea.
The completion of Human Genome Project enabled us to access to the information on nucleotide sequences of whole human genome. One of the most valuable information on human genome would be the list of approximately 35,000 genes. Although 35% of them are still needed to annotate their functions, we can genome-widely approach to various conditions including disease states. To analyze bunch of information at once, we need high-throughput technology containing most of genes. DNA chip successfully provide a stable platform technology for the massive screening of genomes. Microarrays can be used to obtain genome-wide fingerprint on transcriptional changes in various physiological and pathological conditions, leading to the mining novel genes related to those specific states. We can check the multiple molecular markers for diagnosis, prediction or prognosis of specific diseases. Data from microarray will provide huge amounts of experssion profile, which might induce the transformation of biomedical research.
UI - 11708324
AU - Suh Y
TI - [CSNP discovery by two-dimensional gene scanning (TDGS)]
SO - Exp Mol Med 2001 Apr 21;33(1 Suppl):21-47
AD - Metagentech, Co., Ltd., Seoul, Korea.
Challenges in the post-genomic era are to use genetic information in correlating individual gene variations (SNPs; single nucleotide polymorphisms, the most common form of genetic variation) with medically important parameters, such as disease susceptibility, individual responses to drugs and prognostic variables. What is missing is a high-throughput technology to identify all possible SNPs in essentially all human genes in population-based studies with high accuracy and speed in a cost-effective manner. Most tests advocated for their high throughput at low cost are actually SNP screening tests. That is, they screen samples for the presence of one or multiple previously identified SNPs. Such screening methods are only useful when all relevant SNPs in the genes of interest are known, which is presently not the case. Moreover, the usefulness of any one SNP varies enormously from population to population. Indeed, for the Korean population, where no information on possible sequence variation is available, a mutational scanning method, capable to detect all possible gene variations will be most useful. Two-Dimensional Gene Scanning (TDGS) is a high-throughput platform that enables to detect all possible SNPs in an entire gene in one gel under one set of conditions, with high sensitivity and specificity. TDGS is based on automated two-dimensional (2-D) DNA electrophoresis according to size and base pair sequence to detect DNA fragments containing all possible variations. Because the 2-D format permits the analysis of as many as 40 fragments of 250 bp on average in parallel, TDGS allows extensive multiplex PCR (megaplex PCR), i.e. up to 26 fragments in one single reaction, resulting in a significant cost reduction. TDGS tests are designed using a computer program to optimally position PCR primers around the relevant target sequences (exons). A simple automated 2-D instrument allows scanning all exons of a large gene in 8 different samples well within 3 hours. Using three different fluorophores this provides a throughput.
UI - 11708326
AU - Shin HD
TI - [Host genetic epidemiology by single nucleotide polymorphism(SNP) analysis]
SO - Exp Mol Med 2001 Apr 21;33(1 Suppl):51-69
AD - SNP Genetics, Seoul, Korea.
The completion of the whole human genome sequences is now a reality. Emphasis on the analysis of genetic variations on both an individual level and a population level is more important than ever. The identification and characterization of single nucleotide polymorphisms (SNPs) in target genes or candidate genes plays a crucial role in identification of disease genes and in expediting drug discovery/development. Identification of known SNPs can be easily accomplished by searching the ever-expanding public domain databases. However, discovery of new SNPs is best accomplished by sequencing a reasonable subset of the applicable population groups. Particular SNPs of interest will be the ones that affect coding changes and regulatory functions of genes. Once SNPs have been identified, the next step is to examine their frequency in disease models by accurate, cost-effective and high-throughput SNP genotyping methods. This presentation will cover the overview of principal techniques of SNP genotyping which have been developed so far. And also will be discussed the importance of well-defined disease model and error-free high-throughput SNP genotyping in candidate genes and genome-wide SNP screening in the near future.
UI - 11708327
AU - Kang DH
TI - [Molecular and genetic epidemiology]
SO - Exp Mol Med 2001 Apr 21;33(1 Suppl):73-82
AD - Department of Prerentive Medicine, Seoul National Univarsity College of Medicine, Korea.
Molecular epidemiology is defined as "the use of biological markers in epidemiologic research" and genetic epidemiology is defined as "the study of the interaction between genetic and environmental factors in epidemiologic research". Traditional epidemiologic approaches defined as "the study of the distribution and determinants of disease frequency in human population" could not address the importance of genetic susceptibility of humans in disease occurrence. However, the use of biological or genetic markers identified and characterized by the help of advance in molecular biology and human genetics now can provide us better understanding of multi-factorial or multistep disease occurrence in humans. Biological markers used in molecular epidemiology are classified into three groups: biomarkers of exposure (i.e., carcinogen metabolites in human urine, DNA-adducts, etc.), biomarkers of effects (i.e., oncoproteins, tumor markers, etc.), and biomarkers of susceptibility (i.e., genetic polymorphisms of carcinogen metabolism enzymes, DNA repair, etc.). Susceptibility genes involved in disease pathogenesis are categorized into two groups: high penetrance genes (i.e., BRAC1, RB, etc.) and low penetrance genes (i.e., GSTs, XRCC1, etc.). This paper will address the usefulnesses of bomarkers in edpidemiologic research and will show the examples of the use of selected low penetrance genes involved in human carcinogenesis. The importance of multidisciplinary approaches among epidemiologists, molecular biologists, and human geneticists will also be discussed.
UI - 11914929
AU - Karges W; Schaaf L; Dralle H; Boehm BO
TI - Clinical and molecular diagnosis of multiple endocrine neoplasia type 1.
SO - Langenbecks Arch Surg 2002 Mar;386(8):547-52
AD - Division of Endocrinology, Department of Internal Medicine, University of Ulm, Robert Koch Strasse, 89081 Ulm, Germany. firstname.lastname@example.org
Multiple endocrine neoplasia type 1 (MEN1) is a classic hereditary tumor syndrome characterized by a genetic predisposition to develop a variety of neuroendocrine neoplasias and hormone excess syndromes. The disease is caused by inactivating mutations of the MEN1 tumor suppressor gene, detectable in >95% of MEN1 families. The distinction of MEN1-associated tumors from sporadic neuroendocrine neoplasias is clinically important for providing optimal surgical and medical therapy, appropriate clinical follow-up, and counsel for affected patients and their families. Since MEN1 gene analysis became available in 1997, new diagnostic approaches have evolved in clinical management, to be reviewed in this article. Genetic screening of MEN1 families will allow definition of individual disease risk at a preclinical stage, thus helping to allocate medical resources and treatment as individually needed. These new diagnostic approaches are expected to reduce MEN1-associated morbidity and mortality, health care expenses, and psychological disease burden.
UI - 11987443
AU - Chikhaoui Y; Gelinas H; Joseph L; Lance JM
TI - Cost-minimization analysis of genetic testing versus clinical screening of at-risk relatives for familial adenomatous polyposis.
SO - Int J Technol Assess Health Care 2002 Winter;18(1):67-80
AD - Quebec Agency for Health Services and Technology Assessment.
OBJECTIVE: Familial adenomatous polyposis (FAP) is a well-known hereditary colorectal cancer-predisposing syndrome. Genetic testing for colorectal cancer risk is now part of standard medical practice, but very little is known about the economic impact of this technology. The aim of this study was to assess, from a healthcare system perspective, the direct costs of two strategies for screening at-risk relatives of FAP patients: clinical screening versus genetic testing for FAP. METHODS: A systematic review of the literature was carried out. Additional information was gathered from experts in research and clinical laboratories and in hospital departments. A decision tree was constructed to compare per-person and per-family costs of the two strategies for screening at-risk relatives of FAP patients. Sensitivity analysis was performed to assess the stability of the model across the full range of plausible values for all key parameters. RESULTS: According to the decision analysis, with FAP screening starting at puberty, the average screening costs are $3,181 and $2,259 (Canadian dollars), respectively, for the clinical screening and the genetic testing strategies. Genetic screening is cost saving up to a first screening age of 36. Sensitivity analysis shows that the results of the baseline analysis hold across a variety of assumptions concerning the parameter values. CONCLUSIONS: The genetic testing strategy is cost saving relative to the clinical screening alternative. Apart from its lower costs, it is associated with many other benefits. Accordingly, under predefined conditions, predictive genetic testing seems to be the optimal screening strategy for FAP.
UI - 11761722
AU - Rickert CH; Dockhorn-Dworniczak B; Busch G; Moskopp D; Albert FK; Rama
TI - B; Paulus W Increased chromosomal imbalances in recurrent pituitary adenomas.
SO - Acta Neuropathol (Berl) 2001 Dec;102(6):615-20
AD - Institute of Neuropathology, University Clinics Munster, Domagkstr. 19, 48129 Munster, Germany. email@example.com
Eight pituitary adenomas (four gonadotroph cell adenomas, three prolactin cell adenomas, one null cell adenoma) and their respective recurrences in the same patients were studied by comparative genomic hybridization. Chromosomal imbalances were found in seven of eight patients affecting two of eight primary and seven of eight recurrent tumors. Overall, pituitary adenomas showed an average of 1.6 chromosomal imbalances per primary and 3.4 per recurrent tumor (P < 0.01). Prolactin cell adenomas showed an average of 4.3 chromosomal changes per primary and 6.3 per recurrent tumor, which were significantly more common than in gonadotroph cell adenomas (0 vs 1.7 changes; P < 0.05) and the null cell adenoma (0 vs 1.0 changes; P < 0.05). The most common changes were gains of 4q (in three of eight recurrences), 5q, and 13q (in two of eight recurrences each) as well as losses of chromosome 2 (in both primary and recurring tumors of two patients), 1p, 8q, 10, and 12q (in two of eight recurrences). Minimal common regions associated with recurrent adenomas were gains of 4q31.2-34 (three recurrences), 5q14-23 and 13q21-31 and losses of 12q24.3-qter (two recurrences each). The average MIB-1 proliferation indices were 1.2% for primary and 1.9% for recurrent adenomas (P < 0.005). Our findings suggest that acquisition of certain chromosomal imbalances is related to and may underlie adenoma recurrence.
UI - 11877310
AU - Tobin G; Thunberg U; Johnson A; Thorn I; Soderberg O; Hultdin M; Botling
TI - J; Enblad G; Sallstrom J; Sundstrom C; Roos G; Rosenquist R Somatically mutated Ig V(H)3-21 genes characterize a new subset of chronic lymphocytic leukemia.
SO - Blood 2002 Mar 15;99(6):2262-4
AD - Department of Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden.
Recent studies on the immunoglobulin variable heavy chain (IgV(H)) genes have revealed that B-cell chronic lymphocytic leukemia (B-CLL) consists of at least 2 clinical entities with either somatically mutated or unmutated V(H) genes. We have analyzed the V(H) gene mutation status and V(H) gene usage in 119 B-CLL cases and correlated them to overall survival. A novel finding was the preferential use of the V(H)3-21 gene in mutated cases, whereas biased V(H)1-69 gene usage was found in unmutated cases as previously reported. Interestingly, the subset of mutated cases using the V(H)3-21 gene displayed distinctive genotypic/phenotypic characteristics with shorter average length of the complementarity determining region 3 and clonal expression of lambda light chains. In addition, this mutated subset showed significantly shorter survival than other mutated cases and a similar clinical course to unmutated cases. We therefore suggest that B-CLL cases with mutated V(H)3-21 genes may constitute an additional entity of B-CLL.
UI - 11902139
AU - Reid AG; Huntly BJ; Hennig E; Niederwieser D; Campbell LJ; Bown N;
TI - Telford N; Walker H; Grace CD; Deininger MW; Green AR; Nacheva EP Deletions of the derivative chromosome 9 do not account for the poor prognosis associated with Philadelphia-positive acute lymphoblastic leukemia.
SO - Blood 2002 Mar 15;99(6):2274-5
UI - 11897368
AU - Teupser D; Heino N; Wilfert W; Thiery J
TI - Rapid detection of the prion protein M129V polymorphism with the LightCycler.
SO - J Neurosci Methods 2002 Mar 30;115(1):93-6
AD - Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Liebigstr. 27, 04103 Leipzig, Germany. firstname.lastname@example.org
The common single nucleotide polymorphism at codon 129 of the prion protein gene is a key determinant of the genetic susceptibility to Creutzfeldt-Jakob disease (CJD). Recently, a molecular classification of sporadic CJD based on the M129V genotype in conjunction with other determinants was proposed. In the present study, we describe the development and evaluation of a rapid fluorescent-based assay to detect this polymorphism using the LightCycler system. The two polymorphic alleles could be clearly distinguished by their melting points at 52.1 and 60.4 degrees C, representing the 129V and 129M alleles, respectively. These results were confirmed by DNA sequencing. We evaluated our test in 400 patient samples and found no deviations from the expected melting patterns. The calculated allele frequency for the M-allele was 0.66. Thus, we have established a rapid, reliable fluorescent assay for high-throughput detection of the prion protein M129V polymorphism.
UI - 11906302
AU - Huoponen K; Puomila A; Savontaus ML; Mustonen E; Kronqvist E;
TI - Nikoskelainen E Genetic counseling in Leber hereditary optic neuropathy (LHON).
SO - Acta Ophthalmol Scand 2002 Feb;80(1):38-43
AD - Department of Medical Genetics, University of Turku, Finland. email@example.com
PURPOSE: To demonstrate the importance of mitochondrial DNA (mtDNA) analysis in the diagnosis of Leber hereditary optic neuropathy (LHON) and illustrate the difficulties in genetic counseling of the disease. PARTICIPANTS AND METHODS: Ophthalmological and molecular genetic study of one affected and three unaffected members from a family with heteroplasmic ND1/3460 mtDNA mutation associated with LHON. RESULTS: The proband had variable amounts of mutant mtDNA in all his tissues studied, ranging from 58% in blood to 92% in subcutis. The mother had an extremely low amount of mutant mtDNA in her tissues, except for hair roots, which contained only normal mtDNA. No mutant mtDNA could be detected in the proband's unaffected sister and maternal aunt. CONCLUSIONS: Despite her minimal mutation load, the mother of the proband has still transmitted a considerable amount of mutant mtDNA to her son, who is severely affected. Although proband's unaffected sister and maternal aunt had no mutant mtDNA, a theoretical risk that they may transmit the disease to their offspring cannot be excluded.
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