Integrative genomic and gene expression analysis of chromosome 7 identified novel oncogene loci in non-small cell lung cancer.
Lung cancer accounts for over a quarter of cancer deaths, with non-small cell lung cancer (NSCLC) accounting for approximately 80% of cases. Several genome studies have been undertaken in both cell models of NSCLC and clinical samples to identify alterations underlying disease behaviour, and many have identified recurring aberrations of chromosome 7. The presence of recurring chromosome 7 alterations that do not span the well-studied oncogenes EGFR (at 7p11.2) and MET (at 7q31.2) has raised the hypothesis of additional genes on this chromosome that contribute to tumourigenesis. In this study, we demonstrated that multiple loci on chromosome 7 are indeed amplified in NSCLC, and through integrative analysis of gene dosage alterations and parallel gene expression changes, we identified new lung cancer oncogene candidates, including FTSJ2, NUDT1, TAF6, and POLR2J. Activation of these key genes was confirmed in panels of clinical lung tumour tissue as compared with matched normal lung tissue. The detection of gene activation in multiple cohorts of samples strongly supports the presence of key genes involved in lung cancer that are distinct from the EGFR and MET loci on chromosome 7.
Campbell
Jennifer M
JM
Department of Cancer Genetics and Developmental Biology, British Columbia Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z1L3 Canada.
Lockwood
William W
WW
Buys
Timon P H
TP
Chari
Raj
R
Coe
Bradley P
BP
Lam
Stephen
S
Lam
Wan L
WL
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D045744:Cell Line, Tumor; D002897:Chromosomes, Human, Pair 7; D005784:Gene Amplification; D018628:Gene Dosage; D020869:Gene Expression Profiling; D023281:Genomics / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes / Q000502:physiology; D040641:Quantitative Trait Loci