p53 database

p53 database

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p53 mutation and cancer

p53 MUTATIONS IN OVARY CANCER

Schuijer, M. and Berns, E.M. (2003) TP53 and ovarian cancer. Hum Mutat, 21, 285-291..-> Download

Ovarian cancer

Ovarian cancer is the most lethal gynaecological malignancy and it most commonly occurs in postmenopausal women. Ninety per cent of ovarian cancers are derived from the ovarian surface epithelium and these neoplasms are classified into serous, mucinous, endometrioid, clear-cell and transitional-cell types. The molecular pathology of ovarian carcinomas is heterogeneous and involves various putative precursor lesions and multiple pathways of development. The most common subtype, high-grade serous carcinoma, is characterized by p53 mutations, and BRCA1 and/or BRCA2 dysfunction. It most likely arises from epithelium within inclusion cysts or from the surface of the ovary. In contrast, low-grade serous carcinomas are characterized by KRAS or BRAF mutations and appear to arise via an adenoma-borderline-carcinoma sequence. Similarly, mucinous carcinomas have KRAS mutations and probably develop via an adenoma-borderline-carcinoma sequence. Low-grade endometrioid carcinomas, however, are characterized by mutations in PTEN and CTNNB1, and microsatellite instability, and may arise from ovarian endometriosis or borderline endometrioid tumours. High-grade endometrioid carcinomas have similar changes to high-grade serous carcinomas. Clear-cell carcinomas are characterized by mutations of TGFbetaR2 and over-expression of HNF-1beta, and probably arise from ovarian endometriosis. The molecular changes in transitional-cell carcinomas of the ovary remain largely unknown.

Spectrum of p53 mutations in ovary cancer

DISTRIBUTION OF p53 MUTATIONS IN OVARY CANCER

MUTATIONAL EVENTS IN OVARY CANCER

Meta-analysis of p53 loss of function in ovarian cancer. Points ; mean p53 activity as measured by transactivation with the WAF1promoter ; bars , 95 % CI. The mean and 95 % CI of p53 activity for all studies combined for a specific type of cancer is shown on the far left of each graph. Horizontal line, mean of the combined studies. The publication code is indicated on the x-axis : the first number is an anonymous ID for the publication and the second number indicates the number of p53 mutants included in this study. Studies are presented from left to right in decreasing order of number of p53 mutants. The y-axis corresponds to p53 transactivation activity, with a value of 1.5 for the negative control and a value of 2.5 for 100 % of wild-type activity. Only studies with 5 or more p53 mutations are shown on the graph. More information about this statistical analysis can be found in this article: Soussi, T., Asselain, B., Hamroun, D., Kato, S., Ishioka, C., Claustres, M. and Beroud, C. (2006) Meta-analysis of the p53 mutation database for mutant p53 biological activity reveals a methodologic bias in mutation detection. Clin Cancer Res, 12, 62-69. Download the pdf