TY - JOUR
T1 - High-resolution genomic profiles of human lung cancer
AU - Tonon, Giovanni
AU - Wong, Kwok Kin
AU - Maulik, Gautam
AU - Brennan, Cameron
AU - Feng, Bin
AU - Zhang, Yunyu
AU - Khatry, Deepak B.
AU - Protopopov, Alexei
AU - You, Mingjian James
AU - Aguirre, Andrew J.
AU - Martin, Eric S.
AU - Yang, Zhaohui
AU - Ji, Hongbin
AU - Chin, Lynda
AU - DePinho, Ronald A.
PY - 2005/7/5
Y1 - 2005/7/5
N2 - Lung cancer is the leading cause of cancer mortality worldwide, yet there exists a limited view of the genetic lesions driving this disease. In this study, an integrated high-resolution survey of regional amplifications and deletions, coupled with gene-expression profiling of non-small-cell lung cancer subtypes, adenocarcinoma and squamous-cell carcinoma (SCC), identified 93 focal copy-number alterations, of which 21 span <0.5 megabases and contain a median of five genes. Whereas all known lung cancer genes/loci are contained in the dataset, most of these recurrent copy-number alterations are previously uncharacterized and include high-amplitude amplifications and homozygous deletions. Notably, despite their distinct histopathological phenotypes, adenocarcinoma and SCC genomic profiles showed a nearly complete overlap, with only one clear SCC-specific amplicon. Among the few genes residing within this amplicon and showing consistent overexpression in SCC is p63, a known regulator of squamous-cell differentiation. Furthermore, intersection with the published pancreatic cancer comparative genomic hybridization dataset yielded, among others, two focal amplicons on 8p12 and 20q11 common to both cancer types. Integrated DNA-RNA analyses identified WHSC1L1 and TPX2 as two candidates likely targeted for amplification in both pancreatic ductal adenocarcinoma and non-small-cell lung cancer.
AB - Lung cancer is the leading cause of cancer mortality worldwide, yet there exists a limited view of the genetic lesions driving this disease. In this study, an integrated high-resolution survey of regional amplifications and deletions, coupled with gene-expression profiling of non-small-cell lung cancer subtypes, adenocarcinoma and squamous-cell carcinoma (SCC), identified 93 focal copy-number alterations, of which 21 span <0.5 megabases and contain a median of five genes. Whereas all known lung cancer genes/loci are contained in the dataset, most of these recurrent copy-number alterations are previously uncharacterized and include high-amplitude amplifications and homozygous deletions. Notably, despite their distinct histopathological phenotypes, adenocarcinoma and SCC genomic profiles showed a nearly complete overlap, with only one clear SCC-specific amplicon. Among the few genes residing within this amplicon and showing consistent overexpression in SCC is p63, a known regulator of squamous-cell differentiation. Furthermore, intersection with the published pancreatic cancer comparative genomic hybridization dataset yielded, among others, two focal amplicons on 8p12 and 20q11 common to both cancer types. Integrated DNA-RNA analyses identified WHSC1L1 and TPX2 as two candidates likely targeted for amplification in both pancreatic ductal adenocarcinoma and non-small-cell lung cancer.
KW - Array comparative genomic hybridization
KW - Expression profiling
KW - Lung adenocarcinoma
KW - Squamous-cell lung carcinoma
KW - TP73L
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U2 - 10.1073/pnas.0504126102
DO - 10.1073/pnas.0504126102
M3 - Article
C2 - 15983384
AN - SCOPUS:22144433675
SN - 0027-8424
VL - 102
SP - 9625
EP - 9630
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 27
ER -