Molecular and clinical characteristics of MSH6 germline variants detected in colorectal cancer patients

Hiroko Terui, Tetsuhiko Tachikawa, Miho Kakuta, Yoji Nishimura, Toshimasa Yatsuoka, Kensei Yamaguchi, Kei Yura, Kiwamu Akagi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The MSH6 gene is one of the mismatch repair genes involved in Lynch syndrome and its mutations account for 10-20% of Lynch syndrome. Although previous studies suggested that the difference of the geographical region affects the clinical phenotype of Lynch syndrome, there has been no report on the detailed features of Japanese Lynch syndrome patients carrying an MSH6 mutation. The aim of the present study was to investigate the clinical and molecular features of MSH6 mutation carriers in Japan. Surgically resected 1720 colorectal carcinoma specimens were screened by microsatellite instability (MSI) testing and the MSI-high cases were subjected to a germline mutation analysis of the mismatch repair genes MLH1, MSH2 and MSH6. We investigated the clinical and molecular features of the MSH6 variants, such as the family cancer history, pathological findings, immunohistochemistry, methylation status of the MLH1 promoter and BRAF mutation in the colorectal tumor. Furthermore, the impact of the missense variants on MSH6 protein was predicted by using in silico tools. We identified nine novel pathogenic mutations and eight unclassified missense variants. Among the eight missense variants, three were suspected pathogenic by in silico analysis. We also found that most colorectal cancers in the MSH6 mutation carrier were diagnosed after the age of 50 and were localized distally. Furthermore, the mean age at diagnosis of endometrial cancer in Japanese MSH6 mutation carriers (49.2 years) was earlier than previous reports from Western countries (56.5 years). These results may improve the surveillance program for Japanese MSH6 mutation carriers.

Original languageEnglish
Pages (from-to)2909-2916
Number of pages8
JournalOncology Reports
Volume30
Issue number6
DOIs
Publication statusPublished - 2013 Dec
Externally publishedYes

Fingerprint

Colorectal Neoplasms
Hereditary Nonpolyposis Colorectal Neoplasms
Mutation
Microsatellite Instability
DNA Mismatch Repair
Computer Simulation
Genes
Germ-Line Mutation
Endometrial Neoplasms
Methylation
Japan
Immunohistochemistry
Phenotype
Neoplasms
Proteins

Keywords

  • Colorectal cancer
  • Endometrial cancer
  • HNPCC
  • Immunohistochemistry
  • Lynch syndrome
  • Microsatellite instability
  • MSH6

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Terui, H., Tachikawa, T., Kakuta, M., Nishimura, Y., Yatsuoka, T., Yamaguchi, K., ... Akagi, K. (2013). Molecular and clinical characteristics of MSH6 germline variants detected in colorectal cancer patients. Oncology Reports, 30(6), 2909-2916. https://doi.org/10.3892/or.2013.2781

Molecular and clinical characteristics of MSH6 germline variants detected in colorectal cancer patients. / Terui, Hiroko; Tachikawa, Tetsuhiko; Kakuta, Miho; Nishimura, Yoji; Yatsuoka, Toshimasa; Yamaguchi, Kensei; Yura, Kei; Akagi, Kiwamu.

In: Oncology Reports, Vol. 30, No. 6, 12.2013, p. 2909-2916.

Research output: Contribution to journalArticle

Terui, H, Tachikawa, T, Kakuta, M, Nishimura, Y, Yatsuoka, T, Yamaguchi, K, Yura, K & Akagi, K 2013, 'Molecular and clinical characteristics of MSH6 germline variants detected in colorectal cancer patients', Oncology Reports, vol. 30, no. 6, pp. 2909-2916. https://doi.org/10.3892/or.2013.2781
Terui H, Tachikawa T, Kakuta M, Nishimura Y, Yatsuoka T, Yamaguchi K et al. Molecular and clinical characteristics of MSH6 germline variants detected in colorectal cancer patients. Oncology Reports. 2013 Dec;30(6):2909-2916. https://doi.org/10.3892/or.2013.2781
Terui, Hiroko ; Tachikawa, Tetsuhiko ; Kakuta, Miho ; Nishimura, Yoji ; Yatsuoka, Toshimasa ; Yamaguchi, Kensei ; Yura, Kei ; Akagi, Kiwamu. / Molecular and clinical characteristics of MSH6 germline variants detected in colorectal cancer patients. In: Oncology Reports. 2013 ; Vol. 30, No. 6. pp. 2909-2916.
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