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 language | English |
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Pages (from-to) | 3676-3683 |
Number of pages | 8 |
Journal | Cancer Research |
Volume | 76 |
Issue number | 13 |
DOIs | |
State | Published - Jul 1 2016 |
Bibliographical note
Publisher Copyright:© 2016 American Association for Cancer Research.
Funding
This work was supported in part by Molecular Genetics of Cancer training grant T32 CA009299 (Y. Jakubek), Department of Defense (DoD) grant W81XWH-10-1-1007 (I.I. Wistuba and H. Kadara.), Lung Cancer SPORE grant P50CA70907 from the NCI (I.I. Wistuba), Cancer Prevention and Research Institute of Texas (CPRIT) award RP150079 (P. Scheet and H. Kadara), NIH grant R01HG005859 (P. Scheet), and by the Institutional Cancer Center Support Grant CA16672.
Funders | Funder number |
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Institutional Cancer Center Support | CA16672 |
Molecular Genetics of Cancer training grant | T32 CA009299 |
National Institutes of Health (NIH) | |
U.S. Department of Defense | P50CA70907, W81XWH-10-1-1007 |
U.S. Department of Defense | |
National Human Genome Research Institute | R01HG005859 |
National Human Genome Research Institute | |
National Childhood Cancer Registry – National Cancer Institute | |
Cancer Prevention and Research Institute of Texas | RP150079 |
Cancer Prevention and Research Institute of Texas |
ASJC Scopus subject areas
- Oncology
- Cancer Research