The second case with high TML in our study, which is a recurrence from a low-grade tumor, had a mutation signature resembling that of melanoma tumors, and the identified mutation in MSH2 gene suggests that the hypermutator profile in this case could be related to adjuvant temozolomide treatment, similarly to what was described in tumors harboring MSH6 mutation after alkylator chemotherapy.30 Here, MSH2 is linked to melanoma.