Evaluation of germline BRCA1 and BRCA2 mutations in a multi-ethnic Asian cohort of ovarian cancer patients

Hasmad, Hanis Nazihah; Lai, Kah Nyin; Wen, Wei; Park, Daniel J.; Nguyen-Dumont, Tú; Kang, Peter Choon Eng; Thirthagiri, Eswary; Ma'som, Mahirah; Lim, Boon Kiong; Southey, Melissa C.; Woo, Yin Ling; Teo, Soo Hwang

doi:10.1016/j.ygyno.2015.11.001

Cited by 18 publications

(23 citation statements)

References 35 publications

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“…Similarly, the observed frequency of somatic mutations in our cohort (33%) is in line with the published literature (16−40%) [5, 6, 27, 29, 37]. The BRCA mutation rate in endometrioid carcinoma of the ovary is ≤ 10% [8, 28, 33, 34]. Albeit less investigated, a similarly low frequency has been reported for clear cell carcinomas [25, 26, 28, 34], a feature that may explain their generally poor response to platinum-based chemotherapy [38].…”

Section: Discussionsupporting

confidence: 91%

“…By using NGS, we were able to identify deleterious BRCA1/2 mutations in 12.1% of our patients, with germline mutations being evident in 8.1% of the samples. A similar prevalence of germline mutations has been reported in Chinese patients (6.9%) [33], whereas a higher frequency has been observed in Japanese (12.6%) [28] and Western cohorts (13.2−15.3%) [8, 34, 35]. A Korean study found BRCA1/2 mutations in 13.5% of patients who had a negative family history [36].…”

Section: Discussionsupporting

confidence: 64%

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Prevalence and clinical significance ofBRCA1/2germline and somatic mutations in Taiwanese patients with ovarian cancer

Chao

Chang

Lapke³

et al. 2016

Oncotarget

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Germline and somatic BRCA1/2 mutations define a subset of patients with ovarian cancer who may benefit from treatment with poly (ADP-ribose) polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 germline mutations in Taiwanese patients with ovarian cancer are scarce, with the prevalence of somatic mutations being unknown. We aim to investigate the occurrence of BRCA1/2 mutations in 99 Taiwanese patients with ovarian cancer which included serous (n = 46), endometrioid (n = 24), and clear cell (n = 29) carcinomas. BRCA1/2 mutations were identified using next-generation sequencing of formalin-fixed paraffin-embedded tumor samples. Pathogenic variants ( BRCA1 : n = 7; BRCA2 : n = 6) were detected in 12.1% (12/99) of the study patients. Somatic and germline BRCA1/2 mutation rates in serous ovarian cancer are 4/46 (8.7%) and 8/46 (17%), respectively. All of the pathogenic BRCA1/2 mutations were identified in serous carcinoma samples (12/46; 26.1%). One-third (4/12) of the deleterious BRCA1/2 mutations occurred in tumor tissues only (somatic mutations). All of them coexisted with loss of heterozygosity, resulting in biallelic BRCA inactivation. Five novel pathogenic mutations were identified, including four somatic variants ( BRCA1 p.S242fs, BRCA1 p.F989fs, BRCA1 p.G1738fs, and BRCA2 p.D1451fs) and a germline variant ( BRCA2 p.E260fs). We also detected additional six novel mutations (three in BRCA1 and three in BRCA2) with pathogenic potentials. We conclude that BRCA1/2 mutations are common in Taiwanese patients with serous ovarian carcinoma and similar to mutation rates in other ethnic groups. The analysis of BRCA1/2 somatic mutations is crucial for guiding therapeutic decisions in ovarian cancer.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 64%

Prevalence and clinical significance ofBRCA1/2germline and somatic mutations in Taiwanese patients with ovarian cancer

Chao

Chang

Lapke³

et al. 2016

Oncotarget

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“…Multiple logistic regression using these 3 variables revealed that the most significant predictors for germline variants in BRCA1/2 or any of the other tested genes were the HGSC subtype and family history of OC. Predictive significance of the serous histologic subtype for pathogenic BRCA1 / 2 variant-positive patients with OC was also reported in another Asian population [ 11 ]. Identifying pathogenic germline variant carriers among patients with OC will enable appropriate genetic counseling and will also enable these patients, especially those with pathogenic BRCA1 / 2 variant-positive OC, to benefit from targeted therapy.…”

Section: Discussionmentioning

confidence: 69%

“…In some Asian countries including Japan, genetic counseling and genetic testing have hitherto been offered to patients with OC and a family history of OC or breast cancer [ 11 ]. In our cohort, the frequencies of family history of HBOC-related and Lynch syndrome-related cancers were similar between pathogenic germline mutation-positive cases and negative cases ( Supplementary Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer

et al. 2017

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Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1 (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 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). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2. Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

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“…In population‐based studies, BRCAmut is found in 5–15% of all OC cases . More than 40% of identified BRCAmut carriers have no FH . Second, screening practices are not yet consistent .…”

Section: Introductionmentioning

confidence: 99%

BRCA mutation testing for ovarian cancer in the context of available targeted therapy: Survey and consensus of Hong Kong specialists

Kwong

Cheng

Hsue³

et al. 2019

Asia-Pac J Clncl Oncology

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Aims BRCA mutation (BRCAmut) testing is an important tool for the risk assessment, prevention and early diagnosis of breast cancer (BC) and ovarian cancer (OC), and more recently, for determining patient susceptibility to targeted therapy. This study assessed the current BRCAmut testing patterns and explored physicians’ perspectives on the utilities and optimal sequencing of the testing, in order to facilitate and standardize testing practices. Methods Medical specialists in BC and OC in Hong Kong were invited to complete a questionnaire on BRCAmut testing practices. A panel of specialists with extensive BRCAmut testing experience was also convened to develop consensus statements on testing, using the Delphi method and an anonymous electronic voting system. Results The survey respondents (n = 71) recognized family history (FH) of BC and/or OC and an early age of onset as key factors for referring BRCAmut testing. The proportion of respondents who would test all OCs regardless of FH or age, as per the recent international guideline, was low (28.2%). The largest hurdles to testing were the cost, as well as the availability of next‐generation sequencing‐accredited testing and genetic counseling facilities. The panelists suggested that the sequence of somatic testing followed by germline testing may help address both the imminent need of treatment planning and longer term hereditary implications. The potential emotional and financial burdens of BRCAmut testing should be weighed against the potential therapeutic benefits, and the type and timing of testing personalized. Conclusions Accessibility of BRCAmut testing to all at‐risk individuals will be achievable through improvements in testing affordability, as well as widened availability of accredited testing and genetic counseling facilities.

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Evaluation of germline BRCA1 and BRCA2 mutations in a multi-ethnic Asian cohort of ovarian cancer patients

Cited by 18 publications

References 35 publications

Prevalence and clinical significance ofBRCA1/2germline and somatic mutations in Taiwanese patients with ovarian cancer

Prevalence and clinical significance ofBRCA1/2germline and somatic mutations in Taiwanese patients with ovarian cancer

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer

BRCA mutation testing for ovarian cancer in the context of available targeted therapy: Survey and consensus of Hong Kong specialists

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