title: The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer type.
abstract: BACKGROUND
  PIK3CA is one of the genes most frequently mutated in human cancers and it is a potential target for personalized therapy. The aim of this study was to assess the frequency and type of PIK3CA mutations in gastric carcinoma and compare them with their clinical pathological correlates.
  
  
  METHODS
  We analysed 264 gastric cancers, including 39 with microsatellite instability (MSI), for mutations in the two PIK3CA hotspots in exons 9 and 20 by direct sequencing of DNA obtained from microdissected cancer cells.
  
  
  RESULTS
  The cases harbouring mutations were 42 (16%). All were heterozygous missense single base substitutions; the most common was H1047R (26/42; 62%) in exon 20 and the second was Q546K (4/42; 9.5%) in exon 9. All the mutated MSI cases (8/39) carried the H1047R mutation. No other association between PI3KCA mutations and their clinical pathological covariates was found. A metanalysis of the mutations occurring in the same regions presented in 27 publications showed that ratio between exon 20 and exon 9 prevalences was 0.6 (95% CI: 0.5 -0.8) for colon, 1.6 (95% CI: 1.1 -2.3) for breast, 2.7 (95% CI: 1.6 -4.9) for gastric and 4.1 (95% CI: 1.9 -10.3) for endometrial cancer.
  
  
  CONCLUSIONS
  The overall prevalence of PIK3CA mutations implies an important role for PIK3CA in gastric cancer. The lack of association with any clinical-pathological condition suggests that mutations in PIK3CA occur early in the development of cancer. The metanalysis showed that exon-selectivity is an important signature of cancer type reflecting different contexts in which tumours arise.
authors.affiliation: Department of Pathology, Section of Anatomic Pathology, University of Verona, Verona, Italy. stefano.barbi@univr.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Barbi
authors.forename: Ivana
authors.initials: I
authors.lastname: Cataldo
authors.forename: Giovanni
authors.initials: G
authors.lastname: De Manzoni
authors.forename: Samantha
authors.initials: S
authors.lastname: Bersani
authors.forename: Simona
authors.initials: S
authors.lastname: Lamba
authors.forename: Silvia
authors.initials: S
authors.lastname: Mattuzzi
authors.forename: Alberto
authors.initials: A
authors.lastname: Bardelli
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D042282:Microdissection; D018895:Microsatellite Repeats; D008875:Middle Aged; D008957:Models, Genetic; D015999:Multivariate Analysis; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
references.citation: J Pathol. 1999 Mar;187(4):428-32
references.pmid: 10398102
references.citation: Oncogene. 2008 Jun 5;27(25):3539-45
references.pmid: 18193083
references.citation: Cancer Res. 1999 Mar 1;59(5):1090-5
references.pmid: 10070967
references.citation: Cancer Res. 2004 Nov 1;64(21):7678-81
references.pmid: 15520168
references.citation: Cancer Biol Ther. 2004 Aug;3(8):772-5
references.pmid: 15254419
references.citation: Science. 2002 May 31;296(5573):1655-7
references.pmid: 12040186
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):802-7
references.pmid: 15647370
references.citation: Cancer Res. 2005 Dec 1;65(23):10669-73
references.pmid: 16322209
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2652-7
references.pmid: 18268322
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1475-9
references.pmid: 16432179
references.citation: Genes Chromosomes Cancer. 2000 Apr;27(4):403-11
references.pmid: 10719371
references.citation: Eur J Cancer. 2005 Jul;41(11):1649-54
references.pmid: 15994075
references.citation: BMC Cancer. 2005 Mar 23;5:29
references.pmid: 15784156
references.citation: Surgery. 2006 Mar;139(3):347-56
references.pmid: 16546499
references.citation: Cancer Lett. 2008 Mar 8;261(1):120-6
references.pmid: 18180098
references.citation: IARC Sci Publ. 2004;(157):327-49
references.pmid: 15055305
references.citation: Cancer Res. 2004 Aug 1;64(15):5048-50
references.pmid: 15289301
references.citation: Oncogene. 2005 Feb 17;24(8):1477-80
references.pmid: 15608678
references.citation: Annu Rev Biochem. 1998;67:481-507
references.pmid: 9759495
references.citation: Br J Cancer. 2004 Jul 19;91(2):355-8
references.pmid: 15188009
references.citation: Br J Surg. 2001 Mar;88(3):419-25
references.pmid: 11260110
references.citation: Science. 2004 Apr 23;304(5670):554
references.pmid: 15016963
references.citation: Semin Radiat Oncol. 2002 Apr;12(2):162-9
references.pmid: 11979417
references.citation: Hum Mutat. 2008 Feb;29(2):284-8
references.pmid: 18022911
references.citation: Am J Pathol. 2001 Jan;158(1):317-21
references.pmid: 11141506
references.citation: Hum Pathol. 2006 Nov;37(11):1465-72
references.pmid: 16949921
references.citation: Lancet Oncol. 2005 May;6(5):279-86
references.pmid: 15863375
references.citation: J Cancer Res Clin Oncol. 2006 Jan;132(1):45-50
references.pmid: 16217683
references.citation: Clin Cancer Res. 2007 Oct 15;13(20):6064-9
references.pmid: 17947469