Integrative genomic and gene expression analysis of chromosome 7 identified novel oncogene loci in non-small cell lung cancer

摘要: Lung cancer is broadly classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) types, with the latter group accounting for approximately 80% of cases and having an overall 5-year survival rate of~ 15%(Travis et al, 1999). NSCLC is subclassified into multiple subtypes including adenocarcinomas (AC), squamous cell carcinomas (SqCC), and large cell carcinomas (LCC). While DNA sequence mutations and epigenetic alterations have been demonstrated to drive lung cancer oncogene activation (Wilson et al, 2006), changes in gene dosage have consistently been shown to be a major driving force in lung tumors (Lockwood et al, 2008). Although previous work has investigated gene expression dysregulation in lung cancer cells, there have been very few attempts to incorporate the impact of genomic alterations on gene transcription levels (Coe et al, 2006; Tonon et al, 2005; Zhou et al, 2006). Integrative analysis of recurring genomic and gene expression alterations in NSCLC tumours and cell models may be necessary to yield new insight into lung cancer biology.Multiple studies have shown that aberrations in DNA copy number on chromosome 7 occur frequently in lung cancer, and that gain of chromosome 7 has been associated with NSCLC aggressiveness (Pei et al, 2001), a finding consistent with observations from other cancer types (Arslantas et al, 2007; Garcia et al, 2003; Waldman et al, 1991). Both focal regions of DNA amplification and whole chromosome number imbalances have been observed (Balsara & Testa, 2002; Panani & Roussos, 2006; Zojer et al, 2000). Alteration at chromosome 7 is generally …