title: Genetic variations of the A13/A14 repeat located within the EGFR 3' untranslated region have no oncogenic effect in patients with colorectal cancer.
abstract: BACKGROUND
  The EGFR 3' untranslated region (UTR) harbors a polyadenine repeat which is polymorphic (A13/A14) and undergoes somatic deletions in microsatellite instability (MSI) colorectal cancer (CRC). These mutations could be oncogenic in colorectal tissue since they were shown to result into increased EGFR mRNA stability in CRC cell lines.
  
  
  METHODS
  First, we determined in a case control study including 429 CRC patients corresponding to different groups selected or not on age of tumor onset and/or familial history and/or MSI, whether or not, the germline EGFR A13/A14 polymorphism constitutes a genetic risk factor for CRC; second, we investigated the frequency of somatic mutations of this repeat in 179 CRC and their impact on EGFR expression.
  
  
  RESULTS
  No statistically significant difference in allelic frequencies of the EGFR polyA repeat polymorphism was observed between CRC patients and controls. Somatic mutations affecting the EGFR 3'UTR polyA tract were detected in 47/80 (58.8%) MSI CRC versus 0/99 microsatellite stable (MSS) tumors. Comparative analysis in 21 CRC samples of EGFR expression, between tumor and non malignant tissues, using two independent methods showed that somatic mutations of the EGFR polyA repeat did not result into an EGFR mRNA increase.
  
  
  CONCLUSIONS
  Germline and somatic genetic variations occurring within the EGFR 3' UTR polyA tract have no impact on CRC genetic risk and EGFR expression, respectively. Genotyping of the EGFR polyA tract has no clinical utility to identify patients with a high risk for CRC or patients who could benefit from anti-EGFR antibodies.
authors.affiliation: Inserm U1079, Institute for Biomedical Research and Innovation, University of Rouen, 22 Boulevard Gambetta, CS 76183, Rouen Cedex 76183, France.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Sarafan-Vasseur
authors.forename: David
authors.initials: D
authors.lastname: Sefrioui
authors.forename: David
authors.initials: D
authors.lastname: Tougeron
authors.forename: Aude
authors.initials: A
authors.lastname: Lamy
authors.forename: France
authors.initials: F
authors.lastname: Blanchard
authors.forename: Florence
authors.initials: F
authors.lastname: Le Pessot
authors.forename: Frédéric
authors.initials: F
authors.lastname: Di Fiore
authors.forename: Pierre
authors.initials: P
authors.lastname: Michel
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bézieau
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Latouche
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
authors.forename: Richard
authors.initials: R
authors.lastname: Sesboüé
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D011061:Poly A; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D011061:Poly A; D066246:ErbB Receptors
references.citation: Arch Pathol Lab Med. 2012 May;136(5):510-6
references.pmid: 22540299
references.citation: J Clin Oncol. 2010 Mar 1;28(7):1254-61
references.pmid: 20100961
references.citation: J Natl Cancer Inst. 2007 Feb 7;99(3):244-52
references.pmid: 17284719
references.citation: N Engl J Med. 2007 Nov 15;357(20):2040-8
references.pmid: 18003960
references.citation: J Clin Oncol. 2009 Dec 10;27(35):5924-30
references.pmid: 19884556
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3429-31
references.pmid: 12824340
references.citation: J Clin Oncol. 2007 Aug 1;25(22):3230-7
references.pmid: 17664471
references.citation: BMC Cancer. 2009 Aug 27;9:303
references.pmid: 19712476
references.citation: Eur J Hum Genet. 2007 Oct;15(10):1054-62
references.pmid: 17609673
references.citation: Br J Cancer. 2010 Dec 7;103(12):1765-72
references.pmid: 21139621
references.citation: World J Gastroenterol. 2007 Jul 28;13(28):3806-15
references.pmid: 17657834
references.citation: Nucleic Acids Res. 2010 Jul;38(Web Server issue):W368-72
references.pmid: 20501603
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Eur J Cancer. 2010 Jul;46(11):1997-2009
references.pmid: 20413299
references.citation: Br J Cancer. 2011 Feb 1;104(3):488-95
references.pmid: 21206494
references.citation: J Clin Oncol. 2007 May 1;25(13):1658-64
references.pmid: 17470858
references.citation: Science. 2004 Jun 4;304(5676):1497-500
references.pmid: 15118125
references.citation: N Engl J Med. 2009 Apr 2;360(14):1408-17
references.pmid: 19339720
references.citation: Int J Colorectal Dis. 2012 May;27(5):647-56
references.pmid: 22108904
references.citation: Nature. 2012 Jun 28;486(7404):532-6
references.pmid: 22722830
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: BMC Bioinformatics. 2004 Aug 04;5:104
references.pmid: 15294028
references.citation: Cancer Res. 2009 Oct 1;69(19):7811-8
references.pmid: 19789347
references.citation: Bioinformatics. 2006 Jul 15;22(14):e90-8
references.pmid: 16873527
references.citation: Lancet Oncol. 2005 May;6(5):279-86
references.pmid: 15863375
references.citation: N Engl J Med. 2004 Jul 22;351(4):337-45
references.pmid: 15269313
references.citation: N Engl J Med. 2004 May 20;350(21):2129-39
references.pmid: 15118073
references.citation: Clin Cancer Res. 2009 Jul 15;15(14):4531-7
references.pmid: 19584170
references.citation: J Clin Oncol. 2009 Feb 10;27(5):663-71
references.pmid: 19114683
references.citation: J Clin Oncol. 2010 Nov 1;28(31):4697-705
references.pmid: 20921465