Genomic Landscape Established by Allelic Imbalance in the Cancerization Field of a Normal Appearing Airway
Abstract
Visually normal cells adjacent to, and extending from, tumors of the lung may carry molecular alterations characteristics of the tumor itself, an effect referred to as airway field of cancerization. This airway field has been postulated as a model for early events in lung cancer pathogenesis. Yet the genomic landscape of somatically acquired molecular alterations in airway epithelia of lung cancer patients has remained unknown. To begin to fill this void, we sought to comprehensively characterize the genomic architecture of chromosomal alterations inducing allelic imbalance (AI) in the airway field of the most common type of lung tumors, non–small cell lung cancer (NSCLC). To do so, we conducted a genome-wide survey of multiple spatially distributed normal-appearing airways, multiregion tumor specimens, and uninvolved normal tissues or blood from 45 patients with early-stage NSCLC. We detected alterations in airway epithelia from 22 patients, with an increased frequency in NSCLCs of squamous histology. Our data also indicated a spatial gradient of AI in samples at closer proximity to the NSCLC. Chromosome 9 displayed the highest levels of AI and comprised recurrent independent events. Furthermore, the airway field AI included oncogenic gains and tumor suppressor losses in known NSCLC drivers. Our results demonstrate that genome-wide AI is common in the airway field of cancerization, providing insights into early events in the pathogenesis of NSCLC that may comprise targets for early treatment and chemoprevention. Cancer Res; 76(13); 3676–83. ©2016 AACR.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 30, 2016
- Source ID
- 10.1158/0008-5472.can-15-3064
Entities
People
- Avrum E. Spira
- Carmen Behrens
- Cesar Moran
- Chi-wan Chow
- Erik A Ehli
- Gareth Davies
- Humam Kadara
- Ignacio I. Wistuba
- Jerry Fowler
- Jing Huang
- Jing Wang
- Junya Fujimoto
- Li Xu
- Lili Huang
- Melinda Garcia
- Neda Kalhor
- Paul Scheet
- Randa El-zein
- Reza Mehran
- Selina Vattathil
- Shen Li
- Stephen G. Swisher
- Suk-young Yoo
- Wei Lu
- Wenhua Lang
- Yasminka Jakubek
- Zachary T Weber
Organizations
- Boston University
- Cancer Prevention and Research Institute of Texas
- Houston Methodist Hospital
- National Cancer Institute
- National Institutes of Health
- United States Department of Defense
- University of Texas at Austin