EGFR Dinucleotide Repeat Polymorphism as a Prognostic Indicator in Non-small Cell Lung Cancer

Sarita Dubey; Patricia Stephenson; Donna E. Levy; Judith A. Miller; Steven M. Keller; Joan H. Schiller; David H. Johnson; Jill M. Kolesar; Eastern Cooperative Oncology Group

doi:10.1016/S1556-0864(15)31603-8

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EGFR Dinucleotide Repeat Polymorphism as a Prognostic Indicator in Non-small Cell Lung Cancer

Journal article

Open access

Peer reviewed

EGFR Dinucleotide Repeat Polymorphism as a Prognostic Indicator in Non-small Cell Lung Cancer

Sarita Dubey, Patricia Stephenson, Donna E. Levy, Judith A. Miller, Steven M. Keller, Joan H. Schiller, David H. Johnson, Jill M. Kolesar and Eastern Cooperative Oncology Group

Journal of thoracic oncology, Vol.1(5), pp.406-412

06/2006

DOI: 10.1016/S1556-0864(15)31603-8

PMID: 17409891

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Abstract

The epidermal growth factor receptor (EGFR) has been implicated in tumor growth and progression. Intron 1 of the EGFR gene contains a polymorphic simple sequence repeat (SSR) of 14 to 21 CA dinucleotides, the length of which correlates inversely with the level of EGFR transcription. The authors hypothesized that a shorter length of tumor SSR would be associated with poorer survival in patients with non-small cell lung cancer (NSCLC). Patients enrolled in Eastern Cooperative Oncology Group E3590 (a randomized, prospective trial of adjuvant therapy following resection of stages II and IIIa NSCLC) were randomized to radiation or radiation plus chemotherapy. Genomic DNA extracted from resected tumors was amplified for EGFR intron 1 by polymerase chain reaction and sequenced in a 3730XL DNA analyzer. One hundred fifty-seven primary tumors were sequenced, 106 (68%) of which were heterozygous for intron 1. The most common genotypes were allele lengths of 17/19 dinucleotides (17.8%), 17/18 (11.4%), and 19/19 (11.4%). Allele status (homozygous versus heterozygous) did not correlate with race, gender, weight, performance status, histology, stage, or survival. Shorter allele length (≤18 versus >18 CA dinucleotide repeats) was associated with squamous cell histology (p = 0.03). Allele sum of greater than 35 was associated with improved overall survival (log-rank p = 0.03, hazard ratio = 0.66). This is the first study to characterize the EGFR intron 1 SSR polymorphism in NSCLC. Tumors were most commonly heterozygous for SSR length. Squamous histology was associated with a shorter SSR. Longer sequences are associated with improved survival.

Allele

Intron 1

Simple sequence repeat

Details

Title: Subtitle: EGFR Dinucleotide Repeat Polymorphism as a Prognostic Indicator in Non-small Cell Lung Cancer
Creators: Sarita Dubey - University of California, San Francisco
Patricia Stephenson - Dana Farber Cancer Institute, Boston, Massachusetts
Donna E. Levy - Dana Farber Cancer Institute, Boston, Massachusetts
Judith A. Miller - University of Wisconsin-Madison, School of Pharmacy, Madison, Wisconsin
Steven M. Keller - Albert Einstein College of Medicine
Joan H. Schiller - University of Wisconsin Carbone Cancer Center
David H. Johnson - Vanderbilt University
Jill M. Kolesar - University of Wisconsin–Madison
Eastern Cooperative Oncology Group
Resource Type: Journal article
Publication Details: Journal of thoracic oncology, Vol.1(5), pp.406-412
Publisher: Elsevier Inc; NEW YORK
DOI: 10.1016/S1556-0864(15)31603-8
PMID: 17409891
ISSN: 1556-0864
eISSN: 1556-1380
Language: English
Date published: 06/2006
Academic Unit: Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984695790602771

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