Genomic landscape established by allelic imbalance in the cancerization field of a normal appearing airway

Yasminka Jakubek, Wenhua Lang, Selina Vattathil, Melinda Garcia, Li Xu, Lili Huang, Suk Young Yoo, Li Shen, Wei Lu, Chi Wan Chow, Zachary Weber, Gareth Davies, Jing Huang, Carmen Behrens, Neda Kalhor, Cesar Moran, Junya Fujimoto, Reza Mehran, Randa El-Zein, Stephen G. SwisherJing Wang, Jerry Fowler, Avrum E. Spira, Erik A. Ehli, Ignacio I. Wistuba, Paul Scheet, Humam Kadara

Research output: Contribution to journalArticle

20 Scopus citations

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 genomewide 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.

Original languageEnglish (US)
Pages (from-to)3676-3683
Number of pages8
JournalCancer research
Volume76
Issue number13
DOIs
StatePublished - Jul 1 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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