[A Case of Lynch Syndrome with MLH1 Gene Mutation Identified by Comprehensive Genomic Profiling]

The patient was a woman in her 60s. She presented to our hospital following a positive fecal occult blood test. Colonoscopy revealed multiple advanced cancers in the transverse and sigmoid colon. A subtotal colectomy was performed, followed by adjuvant chemotherapy with the CAPOX regimen. Ten months after surgery, distant metastases to the lungs and mediastinal lymph nodes were observed. Comprehensive genomic profiling(CGP)revealed a mutation in the MLH1 gene. Next-generation sequencing of DNA derived from peripheral blood leukocytes identified a heterozygous pathogenic variant in the MLH1 gene, resulting in a diagnosis of Lynch syndrome. Treatment with immune checkpoint inhibitors(ipilimumab plus nivolumab)was initiated. After confirming a reduction in the size of the metastatic lesions, maintenance therapy with nivolumab monotherapy was continued. As of 4 years and 3 months post-surgery, tumor shrinkage has been sustained, with no evidence of new malignancies, recurrence, or metastasis. Given the presence of multiple colorectal cancers, a history of gynecologic malignancy, and a family history of gastrointestinal cancers, this case illustrates the importance of early consideration of hereditary tumors and highlights the clinical utility of genomic medicine.