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 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.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
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E
Rhei
F
F
Bogomolniy
M G
MG
Federici
D L
DL
Maresco
K
K
Offit
M E
ME
Robson
P E
PE
Saigo
J
J
Boyd
D029681:Arabidopsis Proteins; D024682:BRCA2 Protein; D001483:Base Sequence; D003062:Codon; D005091:Exons; D005260:Female; D019398:Genes, BRCA1; D018734:Genes, erbB-2; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D010940:Plant Proteins / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
C097485:AKT2 protein, Arabidopsis; D029681:Arabidopsis Proteins; D024682:BRCA2 Protein; D003062:Codon; D009363:Neoplasm Proteins; D010940:Plant Proteins; D015221:Potassium Channels; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53