Molecular genetic characterization of BRCA1- and BRCA2-linked hereditary ovarian cancers

Hereditary ovarian cancers associated with germline mutations in either BRCA1 or BRCA2 were studied to determine whether somatic mutation of the P53 gene is required for BRCA-linked ovarian tumorigenesis and further, whether the spectrum of additional somatic molecular genetic alterations present in...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1998-08, Vol.58 (15), p.3193-3196
Main Authors: RHEI, E, BOGOMOLNIY, F, FEDERICI, M. G, MARESCO, D. L, OFFIT, K, ROBSON, M. E, SAIGO, P. E, BOYD, J
Format: Article
Language:English
Subjects:
Arabidopsis Proteins
Base Sequence
Biological and medical sciences
BRCA2 Protein
Codon
Exons
Female
Female genital diseases
Genes, BRCA1
Genes, erbB-2
Genes, myc
Genes, p53
Genes, ras
Germ-Line Mutation
Gynecology. Andrology. Obstetrics
Humans
Immunohistochemistry
Medical sciences
Molecular Sequence Data
Neoplasm Proteins - genetics
Ovarian Neoplasms - genetics
Plant Proteins - genetics
Potassium Channels - genetics
Transcription Factors - genetics
Tumor Suppressor Protein p53 - biosynthesis
Tumor Suppressor Protein p53 - genetics
Tumors
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Summary:Hereditary ovarian cancers associated with germline mutations in either BRCA1 or BRCA2 were studied to determine whether somatic mutation of the P53 gene is required for BRCA-linked ovarian tumorigenesis and further, whether the spectrum of additional somatic molecular genetic alterations present in these tumors differs from that known to exist in sporadic ovarian cancers. Forty tumors, 29 linked to BRCA1 and 11 linked to BRCA2, were examined for mutational alterations in P53, K-RAS, ERBB-2, C-MYC, and AKT2. The presence of a P53 mutation in 80% of these cancers indicates that P53 mutation is common but not required for BRCA-linked ovarian tumorigenesis; notably, a significantly higher proportion of the P53 mutations in BRCA2-linked cancers were deletions or insertions compared with the more typical spectrum of missense mutations seen in BRCA1-linked cancers. Additionally, BRCA-linked ovarian carcinomas seem to develop through a unique pathway of tumorigenesis that does not involve mutation of K-RAS or amplification of ERBB-2, C-MYC, or AKT2.
ISSN:0008-5472
1538-7445