The goal of the study is to report the frequency of subsequent BC and high-grade serous carcinoma (HGSC) following RRSO in BRCA1 and BRCA2 mutation carriers and in patients with personal history of BC with or without BRCA mutation.
Little is known regarding the miRNA expression profiles of high grade serous carcinoma in relation to BRCA1/2 status, and compared to normal tubal epithelium, the putative tissue of origin for high grade serous carcinomas.
Here we have used one ID8 Trp53 <sup>-/-</sup> clone to generate further mutants, with additional mutations in Brca1, Pten and Nf1, all of which are frequently mutated or deleted in HGSC.
Overall, 79% of tumors were classified as high-grade serous carcinoma (n=138), and the most common mutations in high-grade serous carcinomas were TP53 (94%), BRCA1 (25%), BRCA2 (11%), and ATM (7%).
If true, an increased incidence of uterine papillary serous carcinomas would be expected in BRCA1 and BRCA2 mutation carriers, who are at high-risk of developing pelvic high-grade serous carcinoma.
Carriers of BRCA1 and BRCA2 mutations are at increased risk of high grade serous carcinoma and are therefore offered risk-reducing salpingo-oophorectomy (RRSO) by 40-45 years.
In one of the four women with co-existing ovarian HGSC and tubal precursor lesion we found non-identical TP53 mutations and a lack of common mutations shared between her precursor lesion and carcinoma.
In all, 103 cases were high-grade serous carcinoma and of these 31 (30%) had germline or somatic BRCA1 or BRCA2 mutations (20% BRCA1 and 10% BRCA2) (group 1), 21 (20%) had methylation of BRCA1 (group 2), and in 51 (50%) there was no BRCA loss (group 3).
Intraepithelial fallopian tube neoplasia is thought to be a precursor lesion to high-grade serous carcinoma of the Müllerian adnexae, particularly in women with BRCA1 or BRCA2 mutations.
Carriers of <i>BRCA1/2</i> or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC).
Molecular Alterations of TP53 are a Defining Feature of Ovarian High-Grade Serous Carcinoma: A Rereview of Cases Lacking TP53 Mutations in The Cancer Genome Atlas Ovarian Study.
Thus, the molecular similarity of BRCA1/2-mutated luteal phase FTE and HGSC likely results from an altered response to luteal phase factors other than progesterone.
Women who have inherited germline mutations of BRCA1/BRCA2 are at increased risk of developing high-grade serous carcinoma, and many of these cancers arise in the distal fimbriated end of the fallopian tube.
We explored the molecular changes in HGSC arising in association with specific BRCA1/BRCA2 somatic or germline mutations and in those with BRCA1 DNA promoter methylation.
Overall, 79% of tumors were classified as high-grade serous carcinoma (n=138), and the most common mutations in high-grade serous carcinomas were TP53 (94%), BRCA1 (25%), BRCA2 (11%), and ATM (7%).
Overall, 79% of tumors were classified as high-grade serous carcinoma (n=138), and the most common mutations in high-grade serous carcinomas were TP53 (94%), BRCA1 (25%), BRCA2 (11%), and ATM (7%).
The goal of the study is to report the frequency of subsequent BC and high-grade serous carcinoma (HGSC) following RRSO in BRCA1 and BRCA2 mutation carriers and in patients with personal history of BC with or without BRCA mutation.
Ovulation is the strongest risk factor for ovarian high-grade serous carcinoma (HGSC) that largely originates from the fallopian tube fimbriae and always carries loss-of-function mutations of TP53 in both early and late lesions.
Novel TP53 in-frame deletion mutations c.719_727delGTTCCTGCA (p53 p.Ser240_Cys242del) and c.634_642delTTTCGACAT (p53 p.F212_H214del) were detected in a single case of HGSC each.