Abstract 1958P
Background
Germline mutations in BRCA1/2 genes are considered major risk factors for hereditary ovarian and breast cancers. In these tumors, the presence of BRCA1/2 alterations is exploited to guide therapy, perform active surveillance and prophylaxis. Recent studies have shown that BRCA1/2 mutations in lung or colorectal cancer may represent a unique clinical entity. Here, we sought to describe the prevalence of somatic BRCA1/2 mutations in an unbiased cohort of cancer patients.
Methods
We retrospectively investigated annotations of somatic BRCA1/2 analysis. DNA was extracted from formalin-fixed paraffin-embedded sections and analyzed using the Ion AmpliSeq Oncomine BRCA assay in the Pathology department. Classification of variants was based on ClinVar and Varsome databases. The study population included cancer patients receiving therapy at the Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center outpatient clinic.
Results
During study period (Q4 2017- Q2 2019), 550 patients underwent somatic BRCA1/2 sequencing; 69% were female, the average age was 57.2, 67.5% were Jewish, and 33% of the study population had documented Ashkenazi ancestry. The six most common cancer diagnoses among study participants were: 119 cases of colorectal cancer, 84 breast cancers, 61 pancreatobiliary tumors, 29 uterine cancers, 36 ovarian cancers, and 20 lung tumors. BRCA1/2 sequencing was normal in about half the tests (49.1%, n=270), 8.7% (n=48) had a pathogenic variant, 14.9% (n=82) had a variant of uncertain significance, and 14.4% (n=79) had a benign variant. In 12.9% (n=71) of the samples, results could not be achieved because of a technical failure. Of the pathogenic variants, 18 were in BRCA1 and 30 in BRCA2. Ashkenazi founder mutations comprised only 29% (n=14) of the pathologic variants. Out of the 48 patients with a pathogenic variation, 32 (66%) were Jewish and half were Ashkenazi (n=23, 48%). The six histologies with the highest prevalence of pathogenic variants were: ovarian (22%), uterine (13.8%), lung (10%), breast (8.3%), pancreatic (8.2%), and colorectal (5.9%).
Conclusions
Testing for somatic BRCA1/2 mutations can identify pathogenic mutations across a wide variety of common malignancies, including lung and colorectal.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.