TY - JOUR
T1 - Genomic landscape established by allelic imbalance in the cancerization field of a normal appearing airway
AU - Jakubek, Yasminka
AU - Lang, Wenhua
AU - Vattathil, Selina
AU - Garcia, Melinda
AU - Xu, Li
AU - Huang, Lili
AU - Yoo, Suk Young
AU - Shen, Li
AU - Lu, Wei
AU - Chow, Chi Wan
AU - Weber, Zachary
AU - Davies, Gareth
AU - Huang, Jing
AU - Behrens, Carmen
AU - Kalhor, Neda
AU - Moran, Cesar
AU - Fujimoto, Junya
AU - Mehran, Reza
AU - El-Zein, Randa
AU - Swisher, Stephen G.
AU - Wang, Jing
AU - Fowler, Jerry
AU - Spira, Avrum E.
AU - Ehli, Erik A.
AU - Wistuba, Ignacio I.
AU - Scheet, Paul
AU - Kadara, Humam
N1 - Funding Information:
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.
Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-15-3064
DO - 10.1158/0008-5472.CAN-15-3064
M3 - Article
C2 - 27216194
AN - SCOPUS:84977484449
SN - 0008-5472
VL - 76
SP - 3676
EP - 3683
JO - Cancer Research
JF - Cancer Research
IS - 13
ER -