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NCI CANCERLIT^® Search: Li-Fraumeni Syndrome - August 2002

Imprima English

National Cancer Institute^®
Ultima Vez Modificado: 1 de agosto del 2002

Identification of a rare polymorphism in the human TP53 promoter.
Analysis of p53 tumor suppressor gene in families with multiple glioma patients.
Genetics of childhood cancer.
The Li-Fraumeni syndrome.

Table of Contents

1
UI - 12127401
AU - Attwooll CL; McGown G; Thorncroft M; Stewart FJ; Birch JM; Varley JM
TI - Identification of a rare polymorphism in the human TP53 promoter.
SO - Cancer Genet Cytogenet 2002 Jun;135(2):165-72
AD - CRC Department of Cancer Genetics, Paterson Institute for Cancer Research, Manchester, UK. cattwooll@deosrv.lar.ieo.it
The majority of families with classic Li-Fraumeni Syndrome (LFS) and a significant proportion of Li-Fraumeni-like (LFL) families have a germline mutation in the TP53 tumor suppressor gene. However around 20% of LFS and 60% of LFL families have no identifiable genetic defect in the coding region or splice junctions of TP53, and the genetic basis for cancer susceptibility in these families remains largely uncharacterized. To determine whether promoter mutations could be responsible for the Li-Fraumeni phenotype, we sequenced the TP53 promoter in index cases from members of classic LFS and LFL families without detectable TP53 mutations. We identified an identical single nucleotide deletion within the C/EBP- like site of the promoter in two out of eighteen such families (11%), compared to only one of a total of 366 control samples (0.3%). Although this result is highly significant (P=0.006, Fischer's exact test), the mutation did not affect the expression of TP53 in our hands. We provide evidence that this site is not utilized in the wild type TP53 promoter and further, that mutation of this site in LFS/LFL does not have a functional effect. We conclude that the sequence variant is a rare polymorphism arising within the TP53 promoter. However, the significantly increased frequency of this variant in LFS/LFL remains intriguing.

2
UI - 11859970
AU - Paunu N; Syrjakoski K; Sankila R; Simola KO; Helen P; Niemela M;
TI - Matikainen M; Isola J; Haapasalo H Analysis of p53 tumor suppressor gene in families with multiple glioma patients.
SO - J Neurooncol 2001 Dec;55(3):159-65
AD - Department of Pathology, Tampere University Hospital and University of Tampere, Finland. niina.paunu@uta.fi
The high incidence of gliomas in Li-Fraumeni families and the high frequency of somatic p53 mutations in sporadic glial tumors have raised the possibility that germline p53 mutations could play an important role in familial aggregation of gliomas. In the present study, 18 families with two or more gliomas were screened for germline p53 mutation. The families were identified through questionnaires sent to 369 consecutive glioma patients operated at Tampere University Hospital during 1983-1994. In these families, a family history of cancer was verified through the Finnish Cancer Registry. Interestingly, the questionnaires reveled only 15 of 57 cancers (index gliomas excluded) retrieved through the Cancer Registry. None of the 18 families fufilled the criteria for classic Li-Fraumeni syndrome. Immunostaining analysis of p53 protein accumulation suggested that alterations of the p53 gene are as common in familial as in sporadic gliomas. Sequencing analysis of exons 4-10 of the p53 gene revealed no germline mutations in any of the 18 families. Thus, although occasional glioma families carrying germline p53 mutations have been identified in earlier studies, systematic evaluation of familial glioma patients suggests that the p53 gene is not a common susceptibility gene in case of familial gliomas. The p53 tumor suppressor gene seems to have a similar role in the tumorigenesis of most familial and sporadic gliomas.

3
UI - 12151885
AU - Ganjavi H; Malkin D
TI - Genetics of childhood cancer.
SO - Clin Orthop 2002 Aug;(401):75-87
AD - Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
In recent years, knowledge of the molecular genetics of childhood cancers has been increasing at an exponential rate. The study of the molecular mechanisms of oncogenesis has led to an understanding of the role that tumor suppressors, oncogenes, and deoxyribonucleic acid (DNA) repair genes play in development of the disease. Chromosomal translocations can lead to the disruption of growth regulatory genes or the formation of growth stimulatory fusion genes in leukemias and solid tumors. These alterations can occur sporadically or can be inherited, which often leads to cancer in children or young adults. Often, the presence of specific genetic alterations can be used to diagnose a cancer that otherwise would be difficult to verify. Genetic mutations also can be prognostic indicators and guide the treatment plan of the physician.

4
UI - 11900879
AU - Chompret A
TI - The Li-Fraumeni syndrome.
SO - Biochimie 2002 Jan;84(1):75-82
AD - Departement de Medecine Institut Gustave-Roussy, Villejuif, France. chompret@igr.fr
Li-Fraumeni syndrome (LFS) has been the most common terminology used for the syndrome. It is a rare familial dominantly inherited cancer syndrome characterized by a wide spectrum of neoplasms occurring in children and young adults. The canonical definition of LFS includes a proband diagnosed with sarcoma before 45 years of age, a first-degree relative with cancer before this same age and another first- or second-degree relative in the lineage with any cancer before this age or sarcoma at any age. Multiple studies have reported p53 germline mutations in LFS families in various parts of the world. As in sporadic tumors, loss of heterozygosity leading to the inactivation of the wild-type allele by deletion or mutation is observed in LFS tumors. Cancer-risk in mutation carriers has been estimated to be 73% in males and nearly 100% in females, the difference almost entirely explained by breast cancer. The identification of germline p53 mutations in rare cancer-prone families has given rise to the medical, counseling, psychological and ethical problems.

The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.

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