Abstract 6461: Prevalence and implications of potentially pathogenic germline variants among adult patients in the Philippines with solid malignancies who underwent tumor genomic profiling: A multi-institutional, cross-sectional study

Abstract Background: In high income countries, 2-10% of tumor genomic profiling reports reveal incidental pathogenic germline variants. A third of these patients would not qualify for genetic testing based on current guidelines. In South East Asia, despite increased use of outsourced genomic profiling platforms, there are no published studies exploring the prevalence of these potentially pathogenic germline variants (PPGV). Our study determined the prevalence of PPGVs among adult patients with solid malignancies who underwent liquid or tissue-based tumor genomic profiling in the Philippines. Methods: Annotated reports of patients with solid cancers who underwent tumor genomic profiling using FoundationOne or FoundationOne Hemebetween January 2021 to July 2023 were reviewed (Ethical Board ID: SL-23143). PPGVs were identified according to recommendations from American Board of Medical Genetics and Genomics and expert review. PPGV criteria include having a variant allele frequency of >30% and were categorized as: 1) high penetrance gene (HP), founder variant (FV), or variant associated with clinical presentation (VA). Cross-checking the pathogenicity through ClinVar database was also done. Results: Out of 446 patients, 13 PPGV variants were found in 50 (11.2%) patients at a median age of 60.5 years. Of these, 28 (54%) had high penetrance (BRCA1, BRCA2, MSH2, MSH6, MLH1, RAD51C, RAD51D), 24 (46%) patients had VA (APC, SMAD4, CDH1, CDKN2A,PTEN) and two patients with lung cancer had a founder variant (EGFR p.Thr790Met). PPGVs were primarily found in colorectal (42% of 50 patients with PPGVs), breast (16%), ovarian (6%) and lung (6%) cancer patients (p<0.001). HP genes were mostly found in females (71.4%, p = 0.03), driven by BRCA1/2 variants (15 females and 2 males). Conclusions: The presence of PPGVs warrants formal genetic counselling and germline testing. Given the similar prevalence of PPGVs in this study compared with data from other countries, and the diagnostic and therapeutic implications of detecting incidental PPGVs, we underscore the need for cancer genetics to be incorporated into standard oncologic care in the Philippines. Citation Format: Paula Isabel Gimena Franco, Frances Victoria Que, Jose Jasper Andal, Daphne Ang. Prevalence and implications of potentially pathogenic germline variants among adult patients in the Philippines with solid malignancies who underwent tumor genomic profiling: A multi-institutional, cross-sectional study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6461.