title: 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.
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Yasminka
authors.initials: Y
authors.lastname: Jakubek
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Lang
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Selina
authors.initials: S
authors.lastname: Vattathil
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Melinda
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Lili
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Suk-Young
authors.initials: SY
authors.lastname: Yoo
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Thoracic Head/Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Chi-Wan
authors.initials: CW
authors.lastname: Chow
authors.affiliation: Avera Institute for Human Genetics, Sioux Falls, South Dakota.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Weber
authors.affiliation: Avera Institute for Human Genetics, Sioux Falls, South Dakota.
authors.forename: Gareth
authors.initials: G
authors.lastname: Davies
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Thoracic Head/Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Carmen
authors.initials: C
authors.lastname: Behrens
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Neda
authors.initials: N
authors.lastname: Kalhor
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Cesar
authors.initials: C
authors.lastname: Moran
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Junya
authors.initials: J
authors.lastname: Fujimoto
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Reza
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Department of Radiology, Houston Methodist Research Institute, Houston, Texas.
authors.forename: Randa
authors.initials: R
authors.lastname: El-Zein
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Swisher
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jerry
authors.initials: J
authors.lastname: Fowler
authors.affiliation: Department of Medicine, Boston University, Boston, Massachusetts.
authors.forename: Avrum E
authors.initials: AE
authors.lastname: Spira
authors.affiliation: Avera Institute for Human Genetics, Sioux Falls, South Dakota.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Ehli
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. The University of Texas Graduate School of Biomedical Sciences (GSBS), Houston, Texas. pascheet@mdanderson.org hkadara@mdanderson.org.
authors.forename: Paul
authors.initials: P
authors.lastname: Scheet
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. The University of Texas Graduate School of Biomedical Sciences (GSBS), Houston, Texas. pascheet@mdanderson.org hkadara@mdanderson.org.
authors.forename: Humam
authors.initials: H
authors.lastname: Kadara
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D022981:Allelic Imbalance; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D005500:Follow-Up Studies; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor