Abstract 1806P
Background
Roughly 10% of breast cancers have an identifiable germline pathogenic variant, the most commonly being in the BRCA1/2 genes. Alterations in other genes, such as PALB2, ATM, CHK2, and RAD51C/D are also associated with increased risk of breast cancer when mutated. Pathogenic variants in these genes are also associated with other cancers. An increasing number of somatic mutations in synthetic lethal genes have been noted in “non-syndromic tumor” types; however, the clinical significance is unknown. We attempted to assess the rate of germline mutations in non-syndromic malignancies with concurrent somatic pathogenic mutations.
Methods
Patients with somatic pathogenic variants in BRCA1/2, PALB2, ATM, CHEK2, or RAD51C/D were identified via database review. Those with breast, ovarian, pancreatic, and prostate were excluded from the analysis. A chart review gathered clinical information and germline testing results. If no germline testing was completed, patients were contacted for single site germline testing by Myriad Genetics, Inc.
Results
Of the 247 patients with somatic mutations, 65 patients had existing germline testing or consented to single site germline variant analysis. This included 16 Black, 1 Hispanic, and 47 white patients. Colon adenocarcinoma was the most prevalent tumor type (40%), followed by NSCLC (19%), gastric adenocarcinoma (7%), bladder cancer (7%), and melanoma (6%). Of the 65 patients analyzed, 20 (13.6%) had germline variants in the corresponding target genes. The germline mutational distribution consisted of 30% BRCA1, 25% BRCA2, 25% ATM, 15% CHEK2, 5% PALB2, and no RAD51C/D. In comparing germline versus somatic variants, similar frequency was seen in BRCA1 (10.2% vs 12.1% respectively), PALB2 (1.7% vs 3.3%), and CHEK2 (5.1% vs 5.6%). However, BRCA2 and ATM variants were noted at higher frequency in the somatic genome, 33.3% BRCA2 and 29.8% ATM, compared with germline variants, 8.5%, and 8.5% respectively.
Conclusions
This small study demonstrates the relative frequency of germline BRCA1/2, PALB2, ATM, and CHEK2 in non-syndromic tumor types. The correlation between germline and somatic variants was most frequently noted for BRCA1, PALB2, and CHEK2.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University of Tennessee Health Sciences Center.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.