Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms

G. Nishikawa, S. Sekine, R. Ogawa, A. Matsubara, T. Mori, H. Taniguchi, R. Kushima, N. Hiraoka, K. Tsuta, H. Tsuda, Y. Kanai

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87 Citations (Scopus)


Background:The molecular basis for the development of appendiceal mucinous tumours, which can be a cause of pseudomyxoma peritonei, remains largely unknown.Methods:Thirty-five appendiceal mucinous neoplasms were analysed for GNAS and KRAS mutations. A functional analysis of mutant GNAS was performed using a colorectal cancer cell line.Results:A mutational analysis identified activating GNAS mutations in 16 of 32 low-grade appendiceal mucinous neoplasms (LAMNs) but in none of three mucinous adenocarcinomas (MACs). KRAS mutations were found in 30 LAMNs and in all MACs. We additionally analysed a total of 186 extra-appendiceal mucinous tumours and found that GNAS mutations were highly prevalent in intraductal papillary mucinous tumours of the pancreas (88%) but were rare or absent in mucinous tumours of the colorectum, ovary, lung and breast (0-9%). The prevalence of KRAS mutations was quite variable among the tumours. The introduction of the mutant GNAS into a colorectal cancer cell line markedly induced MUC2 and MUC5AC expression, but did not promote cell growth either in vitro or in vivo.Conclusion:Activating GNAS mutations are a frequent and characteristic genetic abnormality of LAMN. Mutant GNAS might play a direct role in the prominent mucin production that is a hallmark of LAMN.

Original languageEnglish
Pages (from-to)951-958
Number of pages8
JournalBritish Journal of Cancer
Issue number4
Publication statusPublished - 2013 Mar 5


  • GNAS
  • KRAS
  • low-grade mucinous appendiceal neoplasm

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Nishikawa, G., Sekine, S., Ogawa, R., Matsubara, A., Mori, T., Taniguchi, H., Kushima, R., Hiraoka, N., Tsuta, K., Tsuda, H., & Kanai, Y. (2013). Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms. British Journal of Cancer, 108(4), 951-958.