Cancer Genet. 2025 Aug 25;298-299:39-43. doi: 10.1016/j.cancergen.2025.08.008. Online ahead of print.
ABSTRACT
INTRODUCTION: POT1 tumor predisposition (POT1-TPD) is associated with a spectrum of malignancies due to loss of function mutations in POT1 leading to telomere elongation and genomic instability. Osteosarcoma is the most common primary malignant bone tumor and has a poor prognosis when multifocal.
CASE PRESENTATION: A 15-year-old male was found to have a primary right distal femur osteosarcoma with multiple additional bony sites of disease. A POT1 splice site variant (c.949+1G>C) was identified both somatically and in the germline consistent with POT1-TPD. Despite extensive multifocality, the tumor displayed marked chemosensitivity to standard of care therapy and long-term remission was achieved.
DISCUSSION: Evidence suggests that hereditable alterations in telomeric function including POT1 are enriched in sarcoma susceptibility. Furthermore, hereditary tumor predisposition syndromes often increase osteosarcoma risk including a recent report of five patients with POT1-TPD. Multifocal osteosarcoma is rare, but a few retrospective cohorts suggest dismal prognosis. This report details an adolescent male with presumed POT1-TPD who developed synchronous multifocal osteosarcoma exquisitely sensitive to chemotherapy which may represent a unique phenotype for the syndrome.
PMID:40902353 | DOI:10.1016/j.cancergen.2025.08.008
