title: Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms.
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.
  
  
  CONCLUSIONS
  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.
authors: Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors: G
authors: G
authors: Nishikawa
authors: S
authors: S
authors: Sekine
authors: R
authors: R
authors: Ogawa
authors: A
authors: A
authors: Matsubara
authors: T
authors: T
authors: Mori
authors: H
authors: H
authors: Taniguchi
authors: R
authors: R
authors: Kushima
authors: N
authors: N
authors: Hiraoka
authors: K
authors: K
authors: Tsuta
authors: H
authors: H
authors: Tsuda
authors: Y
authors: Y
authors: Kanai
mesh_terms: D002288:Adenocarcinoma, Mucinous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001063:Appendiceal Neoplasms / Q000235:genetics*; D002864:Chromogranins; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D011905:Genes, ras; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009154:Mutation; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs
references: Am J Physiol Lung Cell Mol Physiol. 2009 Apr;296(4):L684-92
references: 19201815
references: Ann Surg. 2005 Feb;241(2):300-8
references: 15650641
references: J Clin Oncol. 2012 Jul 10;30(20):2449-56
references: 22614976
references: Cancer. 1995 Jan 1;75(1 Suppl):154-70
references: 8000994
references: J Clin Pathol. 2012 Oct;65(10):919-23
references: 22718846
references: Pathology. 2008 Jan;40(1):95-7
references: 18038328
references: J Pathol. 2013 Mar;229(4):579-87
references: 23208952
references: Sci Transl Med. 2011 Jul 20;3(92):92ra66
references: 21775669
references: J Pathol. 2012 Sep;228(1):113-8
references: 22374786
references: Scand J Gastroenterol. 2011 Jul;46(7-8):869-74
references: 21443421
references: Nature. 1989 Aug 31;340(6236):692-6
references: 2549426
references: Sci Rep. 2011;1:161
references: 22355676
references: Mod Pathol. 2002 Jun;15(6):599-605
references: 12065772
references: APMIS. 1991 Jul;99(7):653-6
references: 1648933
references: J Biol Chem. 1993 Jul 5;268(19):13956-61
references: 7686147
references: Am J Physiol. 1989 Mar;256(3 Pt 1):G443-50
references: 2538074
references: Eur J Surg Oncol. 2008 Feb;34(2):196-201
references: 17524597
references: Arch Pathol Lab Med. 2011 Oct;135(10):1261-8
references: 21970481
references: Am J Pathol. 1999 Jun;154(6):1849-55
references: 10362811
references: Science. 1990 Aug 10;249(4969):655-9
references: 2116665
references: Am J Physiol Gastrointest Liver Physiol. 2005 Nov;289(5):G949-59
references: 16227528
references: Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14794-9
references: 15459318
references: Cancer. 1995 Feb 1;75(3):757-68
references: 7828125
references: Am J Surg Pathol. 2003 Aug;27(8):1089-103
references: 12883241
references: Carcinogenesis. 2011 Apr;32(4):622-8
references: 21216847
references: Arch Pathol Lab Med. 2002 Jul;126(7):837-41
references: 12088454