High-resolution genomic profiles of human lung cancer.
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.
Tonon
Giovanni
G
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Wong
Kwok-Kin
KK
Maulik
Gautam
G
Brennan
Cameron
C
Feng
Bin
B
Zhang
Yunyu
Y
Khatry
Deepak B
DB
Protopopov
Alexei
A
You
Mingjian James
MJ
Aguirre
Andrew J
AJ
Martin
Eric S
ES
Yang
Zhaohui
Z
Ji
Hongbin
H
Chin
Lynda
L
Depinho
Ronald A
RA
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D015894:Genome, Human; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; C122167:TPX2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D011495:Histone-Lysine N-Methyltransferase; C432968:NSD3 protein, human