(P 346) DETECTION OF GERMLINE VARIANTS IN PATIENTS DIAGNOSED WITH SOFT TISSUE SARCOMA USING EXPANDED

Objective: Soft tissue sarcomas (STS) typically present as sporadic tumors with only a small percentage thought to be associated with inherited genetic syndromes. However, several factors point to a strong genetic component as STS disproportionately affects younger patients and STS survivors carry an increased lifetime risk of developing a second primary malignancy. Little is known about the true frequency of germline mutations that may drive STS tumorigenesis. The aim of this study is to characterize the prevalence of clinically actionable germline variants (defined as pathogenic or likely pathogenic) among patients with localized STS.

Methods: This is a retrospective review of a protective cohort of 73 consecutive patients with a diagnosis of STS seen at a single, high-volume sarcoma surgical oncology program and referred for genetic counseling and testing from October 2018 to January 2023. The main outcome measure was identification of clinically actionable germline variants.

Results: Of the 73 patients with STS, 4 (5%) did not have a referral order placed and were not tested despite the recommendation for universal testing. 18 (25%) patients were referred but did not undergo testing, 51 (70%) were seen by a genetic counselor and genetic testing was performed. Of the patients tested 45 (88%) where White/Caucasian, 2 (4%) Black/African American, 1 (2%) Asian, 3 (6%) Hispanic. Six (11.7%) has a personal history of a second primary cancer. Of the 51 patients with genetic testing results, 17 patients (33.3%) had a clinically actionable genetic variant in the following genes: CHEK2 (n=5, 9.8%), BRCA2 (n=1, 1.9%), PMS2 (n=1, 1.9%), MUTYH (n=4 7.8%), WRN (n=1, 1%), APC (n=2, 3.9%), NF1 (n=1, 1.9%), RB1 (n=1, 1.9%), and RAD51 (n=1, 1.9%). Of the 17 patients with a clinically actionable variant, 3 (5.8%) had a personal history of a non-STS cancer (CHEK2 gene; breast cancer), 5 (9.8%) had at least one first-degree relative with a history of any cancers. 15 (29.4%) had variants of unknown significance (VUS) and 8 (15.6%) had no identified variants.

Conclusion: Clinically actionable variants were identified in 33.3% of patients with STS who underwent genetic testing. Family history is not predictive for who will harbor a germline mutation. The detection rate of germline mutations in sarcoma is similar to other cancers (ovarian/pancreas) where we perform genetic evaluation on all and should be considered in all STS patients.