Characteristics of colorectal cancer (CRC) patients with BRCA1 and BRCA2 mutations.

606 Background: Between 3-5% of CRC patients have BRCA1/2 pathogenic mutations. This study aims to identify associations between BRCA1 and BRCA2 mutations and clinical characteristics in CRC. Methods: A total of 6396 CRC tumor samples were tested with Next-Generation Sequencing (NGS) on a 592-gene panel, pathogenic or presumed pathogenic variants were counted as mutations (mt). Microsatellite instability (MSI) and tumor mutational burden (TMB) were tested by NGS. Statistical correlations were investigated using ANOVA, Chi-square and t-test. Results: Among tumors sampled, 53% derived from male patients and median age was 60 years. BRCA1 mt were detected in 1.1% (n = 72) of tumors, while BRCA2 in 2.8% (n = 179). BRCA1 mt were more frequent in women (W;65%) than men (M;35%) (p = 0.0019) while no relationship with sex was seen for BRCA2 mt (42% F vs. 58% M). No significant associations with age were noticed. Majority of pathogenic mt in BRCA1 (52%; n = 34) and BRCA2 (62%; n = 103) occurred in MSI-High (MSI-H) cases. MSI-H pts had more frameshift mt in both BRCA1/2 than MSS pts. MSS cases had lower rates of BRCA1 and 2 pathogenic mt (44% and 37%, respectively). Right-sided tumors were significantly associated with BRCA1 (p = 0.0056) and BRCA2 (p < 0.0001) mt in MSI-H cases only. BRCA1/2 mt were associated with higher TMB in all CRCs, including MSI-H and MSS cases (p < 0.001). POLE mt (n = 31) were associated with higher BRCA1/2 mt rates (9.6%, 55% respectively). Among MSS cases with POLE wild-type status, BRCA1 (p = 0.0269) and BRCA2 (p = 0.0151) mt were associated with high TMB and combining both BRCA1/2 mutations led to an even higher TMB (3.6%; p = 0.001). Conclusions: This is the first study to show that BRCA1/2 mutations are more frequent in MSI-H, and independently associated with higher TMB, pathogenic POLE mutations, and right-sided tumors in MSI-H CRCs. Given their relationship with TMB, the presence of BRCA1/2 mutations may be potential predictive biomarkers for checkpoint or PARP inhibitors in CRC, a finding that should be prospectively evaluated.

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Oral Contraceptive Use and Risk of Early-Onset Breast Cancer in Carriers and Noncarriers of BRCA1 and BRCA2 Mutations

Yearbook of Obstetrics Gynecology and Women s Health ◽

10.1016/s1090-798x(08)70471-5 ◽

2006 ◽

Vol 2006 ◽

pp. 269-270

Author(s):

L.P. Shulman

Keyword(s):

Breast Cancer ◽

Oral Contraceptive ◽

Early Onset ◽

Contraceptive Use ◽

Early Onset Breast Cancer ◽

Brca1 And Brca2 ◽

Oral Contraceptive Use ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

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BRCA1 and BRCA2 mutations in ovarian cancer: Covariation with specific cytogenetic features

International Journal of Gynecological Cancer ◽

10.1046/j.1525-1438.2000.010004289.x ◽

2000 ◽

Vol 10 (4) ◽

pp. 289-295 ◽

Cited By ~ 10

Author(s):

A. Koul ◽

S. Malander ◽

N. Loman ◽

T. Pejovic ◽

S. Heim ◽

...

Keyword(s):

Ovarian Cancer ◽

Brca1 And Brca2 ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

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Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom

Diagnostics ◽

10.3390/diagnostics11030547 ◽

2021 ◽

Vol 11 (3) ◽

pp. 547

Author(s):

Iolia Akaev ◽

Siavash Rahimi ◽

Olubukola Onifade ◽

Francis John Edward Gardner ◽

David Castells-Rufas ◽

...

Keyword(s):

Ovarian Cancer ◽

Unknown Origin ◽

Parp Inhibitors ◽

Serous Carcinoma ◽

High Grade ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Epithelial Cancers ◽

Pathogenic Variants ◽

Pathogenic Mutations

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

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A MOLECULAR-BASED APPROACH TO INVESTIGATE BREAST CANCER 1 AND BREAST CANCER 2 STATUS IN OVARIAN CANCER AMONG IRAQI WOMEN

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i7.25217 ◽

2018 ◽

Vol 11 (7) ◽

pp. 199

Author(s):

Muhannad Shweash ◽

Saddam Jumaa Naseer ◽

Maisam Khider Al-anii ◽

Thulfiqar Fawwaz Mutar

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Patients ◽

Gene Mutations ◽

Healthy Controls ◽

Brca1 And Brca2 ◽

First Degree Relatives ◽

Brca Gene ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

Objective: Cancer ovary is one of the fatal gynecologic malignancies worldwide. Since breast cancer (BRCA) genes are considered tumor suppressor genes and play important roles in cancer by repairing of chromosomal damage with the error repair of DNA breaks. Therefore, breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene mutations strongly enhance the development of ovarian cancer risk among women. Here, we report that both genes are an essential mediator of progress ovarian cancer, to determine the influence of BRCA1 and BRCA2 mutations in the improvement of ovarian cancer.Methods: A total of 25 subjects were chosen for the genetic studies, and three groups were recruited: fifteen ovarian cancer patients group, five healthy controls, and five first-degree relatives to a known case of ovarian cancer patients.Results: A genetic analysis revealed that a strong correlation exists between both gene mutations’ status in ovarian cancer, and BRCA gene mutations (185delAG, 5382insC, and 4153delA in BRCA1 and 6174delT in BRCA2) remained to establish to have a relatively high frequency among people in this study among ovarian cancer patients. Furthermore, seven patients with ovarian cancer carried all of the four investigated mutations, and five had three mutations.Conclusion: Otherwise, BRCA gene frequency showed low prevalence among first-degree relatives, and to a lesser extent among healthy controls, with only a few had all of the mutations combined. These data demonstrate for the first time a molecular link between BRCA1 and BRCA2 mutations in ovarian cancer progression in Iraq.

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Ratio of female to male offspring of women tested for BRCA1 and BRCA2 mutations

Journal of Medical Genetics ◽

10.1136/jmg.2004.019687 ◽

2004 ◽

Vol 41 (8) ◽

pp. e103-e103 ◽

Cited By ~ 5

Author(s):

K Kotar

Keyword(s):

Male Offspring ◽

Brca1 And Brca2 ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

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Clinical implications of genetic testing for BRCA1 and BRCA2 mutations in Austria

Clinical Genetics ◽

10.1111/cge.12216 ◽

2013 ◽

Vol 85 (1) ◽

pp. 72-75 ◽

Cited By ~ 6

Author(s):

CF Singer ◽

D Muhr ◽

C Rappaport ◽

M-K Tea ◽

D Gschwantler-Kaulich ◽

...

Keyword(s):

Genetic Testing ◽

Clinical Implications ◽

Brca1 And Brca2 ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

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Management of hereditary ovarian cancer

Orvosi Hetilap ◽

10.1556/oh.2011.29218 ◽

2011 ◽

Vol 152 (40) ◽

pp. 1596-1608 ◽

Cited By ~ 2

Author(s):

József Gábor Joó ◽

Szabolcs Ládi ◽

B. Zsolt Nagy ◽

Zoltán Langmár

Keyword(s):

Ovarian Cancer ◽

Hereditary Ovarian Cancer ◽

Brca1 And Brca2 ◽

Ovarian Cancers ◽

Brca2 Mutations ◽

Histological Phenotype ◽

Brca1 Brca2 ◽

Brca1 And Brca2 Mutations ◽

High Level ◽

Associated Tumors

Mutations in BRCA1 and BRCA2 genes account for the majority of hereditary breast and ovarian cancers. Approximately 10% of cases of ovarian cancer are due to germline mutations in BRCA1 and BRCA2. Ovarian cancer associated with BRCA1 and BRCA2 mutations has a distinct histological phenotype. This type of cancer is predominantly of serous or endometrioid histology and is high grade. Patients with BRCA1 or BRCA2 mutations should be offered risk-reducing salpingo-oophorectomy by age 40 years, or when childbearing is complete. Nowadays there are no differences between the treatments provided for sporadic and hereditary ovarian cancer, although there are indications that targeted therapy is effective in women with BRCA1/BRCA2-associated tumors. Retrospective studies reveal a high level of sensitivity to platinum agents in BRCA-associated tumors and initial trials show good efficacy and tolerability for polyADP-ribose polymerase inhibitors in mutation carriers with advanced ovarian cancers. These agents might also potentially be used in chemoprevention. Authors review the current management of hereditary ovarian cancer. Orv. Hetil., 2011, 152, 1596–1608.

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