Cancer occurs through the accumulation of genetic defects, such as amplifications, deletions and loss of heterozygosity (LOH) that can lead to the activation of oncogenes and the inactivation of tumor suppressor genes. Our preliminary studies have shown LOH and copy number information can be extracted from single nucleotide polymorphism (SNP) array analysis and we have re-identified previously reported oncogenes and tumor suppressor gene loci. We propose that higher density SNP arrays can identify smaller regions of amplification, deletion and LOH and this will identify novel oncogenes and tumor suppressor genes involved in lung adenocarcinoma tumorigenesis, as well as provide a molecular basis for tumor classification. To test these proposals, we will aim to (1) identify amplified and deleted regions by surveying LOH and copy number changes of several cancer types using high density SNP arrays, (2) validate novel amplified regions in primary tumor samples using real-time PCR, (3) classify tumor subtypes based on chromosomal alterations, (4) identify the likely gene targets of copy number alteration by integrating datasets and (5) identify potential oncogenes and tumor suppressor genes. ? ? ?
| Carter, Scott L; Cibulskis, Kristian; Helman, Elena et al. (2012) Absolute quantification of somatic DNA alterations in human cancer. Nat Biotechnol 30:413-21 |
| Weir, Barbara A; Woo, Michele S; Getz, Gad et al. (2007) Characterizing the cancer genome in lung adenocarcinoma. Nature 450:893-8 |
