title: Somatic deletions of the polyA tract in the 3' untranslated region of epidermal growth factor receptor are common in microsatellite instability-high endometrial and colorectal carcinomas.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) is overexpressed in up to 80% of colorectal and endometrial carcinomas. Deletions of the polyA tract in the 3' untranslated region (3' UTR) have been reported in microsatellite instability-high (MSI-H) colonic carcinomas, but their impacts on EGFR expression and downstream pathways are unclear. This phenomenon has not been reported in other MSI-H tumors.
  
  
  OBJECTIVE
  To assess the 3' UTR polyA tract of EGFR in both endometrial and colorectal carcinomas and the mutational status of EGFR downstream pathways.
  
  
  METHODS
  Ninety-eight colorectal carcinomas and 47 endometrial carcinomas were included. EGFR 3' UTR polyA status was detected by capillary electrophoresis and Sanger sequencing. EGFR gene expression, EGFR copy numbers, and KRAS and BRAF mutation status were analyzed accordingly.
  
  
  RESULTS
  The 3' UTR polyA tract was deleted in 18 of 23 (78%) MSI-H versus 0 of 24 microsatellite-stable endometrial carcinomas (P < .001). Similar observations were seen in colorectal carcinomas, in which 29 of 36 (81%) MSI-H, 1 of 62 (1.6%) microsatellite instability-low, and none of the microsatellite-stable tumors harbored the deletion (P < .001). A moderate increase in EGFR mRNA level was observed in endometrial carcinomas with 3' UTR polyA deletions versus those with wild-type polyA tract. Amplification of the EGFR gene was not observed. Deletions in polyA tract do not seem to affect the frequency of KRAS and BRAF mutations.
  
  
  CONCLUSIONS
  Deletions of EGFR 3' UTR polyA are frequent in endometrial and colorectal carcinomas, are confined almost exclusively to MSI-H tumors, and do not affect KRAS and BRAF mutations.
authors.affiliation: Division of Pathology and Laboratory Medicine, University of Texas M. D. Anderson Cancer Center, 8515 Fannin Street, Houston, TX 77054, USA.
authors.forename: Ma
authors.initials: M
authors.lastname: Deqin
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.forename: Christopher
authors.initials: C
authors.lastname: Nero
authors.forename: Keyur P
authors.initials: KP
authors.lastname: Patel
authors.forename: Emad M
authors.initials: EM
authors.lastname: Daoud
authors.forename: Hanyin
authors.initials: H
authors.lastname: Cheng
authors.forename: Bojana
authors.initials: B
authors.lastname: Djordjevic
authors.forename: Russell R
authors.initials: RR
authors.lastname: Broaddus
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D042282:Microdissection; D053842:Microsatellite Instability; D008969:Molecular Sequence Data; D009154:Mutation; D011061:Poly A / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D060888:Real-Time Polymerase Chain Reaction; D017384:Sequence Deletion; D018631:ras Proteins / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011061:Poly A; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins