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, Yae Kanai

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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
Volume108
Issue number4
DOIs
Publication statusPublished - 2013 Mar 5
Externally publishedYes

Fingerprint

Appendiceal Neoplasms
Mutation
Mucinous Adenocarcinoma
Neoplasms
Colorectal Neoplasms
Pseudomyxoma Peritonei
Cell Line
Mucins
Pancreas
Ovary
Breast
Lung
Growth

Keywords

  • GNAS
  • KRAS
  • low-grade mucinous appendiceal neoplasm

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nishikawa, G., Sekine, S., Ogawa, R., Matsubara, A., Mori, T., Taniguchi, H., ... Kanai, Y. (2013). Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms. British Journal of Cancer, 108(4), 951-958. https://doi.org/10.1038/bjc.2013.47

Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms. / Nishikawa, G.; Sekine, S.; Ogawa, R.; Matsubara, A.; Mori, T.; Taniguchi, H.; Kushima, R.; Hiraoka, N.; Tsuta, K.; Tsuda, H.; Kanai, Yae.

In: British Journal of Cancer, Vol. 108, No. 4, 05.03.2013, p. 951-958.

Research output: Contribution to journalArticle

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, vol. 108, no. 4, pp. 951-958. https://doi.org/10.1038/bjc.2013.47
Nishikawa G, Sekine S, Ogawa R, Matsubara A, Mori T, Taniguchi H et al. Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms. British Journal of Cancer. 2013 Mar 5;108(4):951-958. https://doi.org/10.1038/bjc.2013.47
Nishikawa, G. ; Sekine, S. ; Ogawa, R. ; Matsubara, A. ; Mori, T. ; Taniguchi, H. ; Kushima, R. ; Hiraoka, N. ; Tsuta, K. ; Tsuda, H. ; Kanai, Yae. / Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms. In: British Journal of Cancer. 2013 ; Vol. 108, No. 4. pp. 951-958.
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abstract = "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.",
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AU - Taniguchi, H.

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