Short Report: The Variants in in Metastatic Uveal Melanoma.

Uveal melanoma (UM) is a rare subtype of melanoma with distinct clinical and molecular features compared to other melanoma subtypes. UM tumors are frequently detected with mutations in , , , , and instead of the typical mutations associated with cutaneous melanoma. Although hereditary UM is rare, germline loss predisposes patients to UM and various other cancers. The (Checkpoint kinase 2) gene that encodes the protein CHK2, a serine-threonine kinase, is a cell cycle checkpoint regulator that acts as a tumor suppressor. CHK2 is involved in DNA repair, cell cycle arrest, or apoptosis in response to DNA damage. mutations have been linked to various cancers. While there is no strong evidence that mutations increase the risk of melanoma, two cases of germline mutations in UM patients have been reported. However, the incidence of variants in metastatic UM (MUM) has not been investigated. Thus, we conducted a retrospective analysis of patients with MUM and variants to understand this link better. We collected MUM cases from 2016 to 2024 from institutional databases. Tissues underwent analyses of molecular and genomic features, including tumor mutational burden, and were performed by a Clinically Certified Laboratory. Next-generation sequencing and variant calling were conducted to identify variants. In this study, we reported ten patients with variants among 740 metastatic UM patients (1.4%) and four primary UM patients with germline mutations. Although rare, UM patients with an abnormal ATM-CHEK2 axis might receive clinical benefits from medications that target DNA repair mechanisms.