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

Deqin Ma; Zhao Chen; Christopher Nero; Keyur P Patel; Emad M Daoud; Hanyin Cheng; Bojana Djordjevic; Russell R Broaddus; L Jeffrey Medeiros; Asif Rashid; Rajyalakshmi Luthra

doi:10.5858/arpa.2010-0638-OA

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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

Journal article

Peer reviewed

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

Deqin Ma, Zhao Chen, Christopher Nero, Keyur P Patel, Emad M Daoud, Hanyin Cheng, Bojana Djordjevic, Russell R Broaddus, L Jeffrey Medeiros, Asif Rashid, …

Archives of pathology & laboratory medicine (1976), Vol.136(5), pp.510-516

05/2012

DOI: 10.5858/arpa.2010-0638-OA

PMCID: PMC3807134

PMID: 22540299

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Abstract

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. To assess the 3' UTR polyA tract of EGFR in both endometrial and colorectal carcinomas and the mutational status of EGFR downstream pathways. 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. 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. 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.

Mutation

Sequence Deletion

ras Proteins - genetics

Microsatellite Instability

Proto-Oncogene Proteins p21(ras)

Microdissection

Colorectal Neoplasms - genetics

Genes, erbB-1 - genetics

Humans

3' Untranslated Regions - genetics

Molecular Sequence Data

Proto-Oncogene Proteins - genetics

Poly A - genetics

Endometrial Neoplasms - genetics

Proto-Oncogene Proteins B-raf - genetics

Base Sequence

Female

Real-Time Polymerase Chain Reaction

Details

Title: Subtitle: 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
Creators: Deqin Ma - Division of Pathology and Laboratory Medicine, University of Texas M. D. Anderson Cancer Center, 8515 Fannin Street, Houston, TX 77054, USA
Zhao Chen
Christopher Nero
Keyur P Patel
Emad M Daoud
Hanyin Cheng
Bojana Djordjevic
Russell R Broaddus
L Jeffrey Medeiros
Asif Rashid
Rajyalakshmi Luthra
Resource Type: Journal article
Publication Details: Archives of pathology & laboratory medicine (1976), Vol.136(5), pp.510-516
DOI: 10.5858/arpa.2010-0638-OA
PMID: 22540299
PMCID: PMC3807134
NLM abbreviation: Arch Pathol Lab Med
ISSN: 0003-9985
eISSN: 1543-2165
Publisher: United States
Grant note: P01 CA130821 / NCI NIH HHS P50 CA098258 / NCI NIH HHS P30 CA016672 / NCI NIH HHS 1P50CA098258-01 / NCI NIH HHS
Language: English
Date published: 05/2012
Academic Unit: Pathology
Record Identifier: 9984047672802771

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