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 language | English |
|---|---|
| Pages (from-to) | 951-958 |
| Number of pages | 8 |
| Journal | British Journal of Cancer |
| Volume | 108 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2013 Mar 5 |
| Externally published | Yes |
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Keywords
- GNAS
- KRAS
- low-grade mucinous appendiceal neoplasm
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms
AU - Nishikawa, G.
AU - Sekine, S.
AU - Ogawa, R.
AU - Matsubara, A.
AU - Mori, T.
AU - Taniguchi, H.
AU - Kushima, R.
AU - Hiraoka, N.
AU - Tsuta, K.
AU - Tsuda, H.
AU - Kanai, Yae
PY - 2013/3/5
Y1 - 2013/3/5
N2 - 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.
AB - 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.
KW - GNAS
KW - KRAS
KW - low-grade mucinous appendiceal neoplasm
UR - http://www.scopus.com/inward/record.url?scp=84875228843&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875228843&partnerID=8YFLogxK
U2 - 10.1038/bjc.2013.47
DO - 10.1038/bjc.2013.47
M3 - Article
VL - 108
SP - 951
EP - 958
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 4
ER -