Lab Med Qual Assur.  2019 Dec;41(4):220-224. 10.15263/jlmqa.2019.41.4.220.

A Case of Lynch Syndrome with the Deletion of Multiple Exons of the MLH1 Gene, Detected by Next-Generation Sequencing

Affiliations
  • 1Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. wlee1@amc.seoul.kr
  • 2Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 3Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 4Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Abstract

A 26-year-old man underwent colonoscopy to investigate weight loss and a lesion suspicious 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 adenocarcinoma 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.

Keyword

DNA copy number variation; MLH1; Next-generation sequencing

MeSH Terms

Adenocarcinoma
Adult
Biopsy
Carcinoma, Hepatocellular
Colon
Colon, Sigmoid
Colonoscopy
Colorectal Neoplasms
Colorectal Neoplasms, Hereditary Nonpolyposis*
DNA Copy Number Variations
Exons*
Genetic Diseases, Inborn
Genetic Testing
Germ-Line Mutation
Humans
Microsatellite Instability
Multiplex Polymerase Chain Reaction
Weight Loss
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