130P Clinicopathologic determinants of prognosis in head and neck soft tissue sarcomas: A multi-factorial survival analysis

specimens (data sourced from MSKCC, Nat Commun 2022).Clinical data for all patients harboring pathogenic POT1 variants were extracted.Results: Pathogenic POT1 mutations were identified in 3% (9/301) of AS patients.Among these, only one mutation (I78T) was a germline mutation associated with familial melanoma, while the remaining eight were somatic splice-site mutations resulting in a truncated protein.The primary tumor sites included skin in four patients and parotid gland, spleen, and pleura in one patient each.The median age of patients was 62 years (range 46e81), and 7 of 9 patients were male.Co-mutations in TP53 were observed in 6/8 cases, while no significant associations with other genes were noted.Somatic truncating mutations in POT1 were the predominant finding.Conclusions: Our findings show that somatic POT1 mutations are predominantly truncating, resulting in POT1 loss, while germline POT1 mutations are typically point mutations causing missense changes.We propose that germline truncating POT1 mutations are not compatible with life and, therefore, are not associated with POT1-TPD.This observation should be validated in a larger AS cohort and may facilitate the identification of inherited cases of AS.