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Published on: July 25, 2020
Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma
Gad Singer1, Robert Oldt, Yoram Cohen
1Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Abstract:
Activating mutations in KRAS and in one of its downstream mediators, BRAF, have been identified in a variety of human cancers. To determine the role of mutations in BRAF and KRAS in ovarian carcinoma, we analyzed both genes for three common mutations (at codon 599 of BRAF and codons 12 and 13 of KRAS). Mutations in either codon 599 of BRAF or codons 12 and 13 of KRAS occurred in 15 of 22 (68%) invasive micropapillary serous carcinomas (MPSCs; low-grade tumors) and in 31 of 51 (61%) serous borderline tumors (precursor lesions to invasive MPSCs). None of the tumors contained a mutation in both BRAF and KRAS. In contrast, none of the 72 conventional aggressive high-grade serous carcinomas analyzed contained the BRAF codon 599 mutation or either of the two KRAS mutations. The apparent restriction of these BRAF and KRAS mutations to low-grade serous ovarian carcinoma and its precursors suggests that low-grade and high-grade ovarian serous carcinomas develop through independent pathways.
Insights
Activating mutations in BRAF and KRAS genes are common in low-grade serous ovarian carcinoma and its precursors. High-grade serous carcinomas lack these specific mutations, suggesting distinct developmental pathways.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Activating mutations in KRAS and BRAF are implicated in various cancers.
- Ovarian carcinoma is a significant health concern, with distinct subtypes.
Purpose of the Study:
- To investigate the role of specific BRAF and KRAS mutations in ovarian carcinoma.
- To differentiate molecular pathways between low-grade and high-grade serous ovarian carcinomas.
Main Methods:
- Analysis of BRAF codon 599 and KRAS codons 12/13 mutations.
- Genomic analysis of invasive micropapillary serous carcinomas (MPSCs), serous borderline tumors, and conventional high-grade serous carcinomas.
Main Results:
- Mutations in BRAF or KRAS were found in 68% of MPSCs and 61% of serous borderline tumors.
- No co-mutations of BRAF and KRAS were observed.
- Conventional high-grade serous carcinomas lacked the analyzed BRAF and KRAS mutations.
Conclusions:
- The specific BRAF and KRAS mutations are predominantly found in low-grade serous ovarian carcinoma and its precursors.
- Low-grade and high-grade serous ovarian carcinomas likely arise from independent molecular pathways.
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