ABSTRACT
Background: Tumor next generation sequencing (NGS) is used to identify somatic mutations. It can also identify potential germline mutations associated with cancer susceptibility. We aimed to describe the frequency of actionable tumor NGS results that met ESMO 2019 guidelines for germline genetic testing (GT), germline GT receipt and positive GT results in a large cancer cohort. Methods: Patients with tumor NGS from Sept 2019-Feb 2022 in a large health system in New York City were retrospectively identified. ESMO guidelines were used to identify potentially actionable germline mutations on NGS (Mandelker et al. 2019). Results: Of 3796 patients who underwent tumor NGS, 454 (12.0%) had at least one potential actionable germline mutation per ESMO guidelines. Cancer types with over 20% of patients whose tumor NGS results met ESMO criteria for germline GT included ampullary, ovarian, uterine, liver, skin, mesothelioma, and thyroid. The most common tumor mutations identified were BRCA2 [26.7%, 95% confidence interval (CI) 22.6-31.0], BRCA1 [14.1%, CI 11.0-17.6], MUTYH [9.9%, CI 7.3-13.0], MSH6 [7.9%, CI 5.6-10.8], and TSC2 [6.8%, CI 4.7-9.6]. Overall, 162 (35.7%) eligible patients per ESMO guidelines received germline GT, of which the most likely cancer types were ovarian (91.1%), pancreatic (66.7%), breast (58.3%), thyroid (50.0%), and uterine (46.9%) (Table). Of 162 patients who underwent germline GT, 98 (60.5%) had positive GT results with the most common cancer types being bone marrow (100%), esophageal (100%), ovarian (80.5%), pancreatic (66.7%) and lung (64.3%). Distribution of positive GT results was: 39 BRCA2;24 BRCA1;12 MUTYH;6 BRIP1;4 RAD51C;4 PALB2;3 MSH6;2 CHEK2;2 MSH2;2 RAD51D;and one each of SDHA, MLH1, NF1, PMS2. [Formula presented] Conclusions: Of 12% of patients who met ESMO criteria for germline GT, only 35% received GT and among those tested, 60% had a germline mutation. Mutations were prevalent across cancer types, highlighting the need for clinicians to know and implement society guidelines. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: B. Pothuri: Non-Financial Interests, Personal, Leadership Role, Clinical Practice Committee Chair, Board of Directors, COVID-19 Taskforce Co-chair: Society of Gynecologic Oncology;Non-Financial Interests, Personal, Leadership Role: Gynecologic Oncology Group;Non-Financial Interests, Personal, Leadership Role, Society Secretary: New York Obstetrical Society;Financial Interests, Personal and Institutional, Advisory Board, Advisory board consulting fee + clinical trial support at NYU: Clovis Oncology, AstraZeneca, Eisai, Sutro, Tesaro/GSK, Merck, Mersana, Seattle Genetics, Toray;Financial Interests, Personal, Advisory Board, Advisory board consulting fee, support for attending meetings: Gynecologic Oncology Group;Financial Interests, Personal, Advisory Board, Advisory board consulting fee: Lilly, Atossa, Elevar, Deciphera, Imab, Arquer Diagnostics;Financial Interests, Personal, Speaker’s Bureau: Bioascend, PERS, Vanium, OncLive;Financial Interests, Institutional, Funding, clinical trial support at NYU: Karyopharm, Immunogen, VBL Therapeutics, Roche/Genentech, Celsion, Takeda, Incyte. All other authors have declared no conflicts of interest.