A 26-year-old man underwent colonoscopy to investigate weight loss and a lesion suspi- cious of colorectal cancer was detected. He had a family history of colorectal cancer and hepatocellular carcinoma. The biopsy result of the lesion showed a well-differentiated adeno- carcinoma of the sigmoid colon and he underwent curative anterior resection of the colon. A microsatellite instability (MSI) test was performed on the resected tumor tissue specimen and it was found to be MSI-high. A next-generation sequencing (NGS)-based hereditary tumor panel test was performed on his peripheral blood to detect the causative germline variant. Neither a pathogenic variant nor a variant of uncertain significance was found in the single nucleotide variant (SNV) and small indel variant analyses. However, a copy number variation (CNV) detection algorithm identified a variant compatible with the deletion of exon 7 to exon 19 of the MLH1 gene. This finding was confirmed to be a true deletion by multiplex ligation-dependent probe amplification. Therefore, the deletion of exon 7 to exon 19 of the MLH1 gene was regarded as the causative pathogenic genetic variant for his colorectal cancer and familial genetic testing was recommended. Therefore, patients with suspected cancer syndromes, including hereditary colorectal cancer, should be tested for germline mutations including CNVs, SNVs, and indels. NGS is a technique that can simultaneously detect SNVs and CNVs and therefore, it has clinical utility for genetic testing for hereditary diseases.

Keywords: DNA copy number variation, MLH1, Next-generation sequencing