CNV assessments associated with outcome distinctions for adult and pediatric cancers: Loss of BRCA1 in neuroblastoma associates with a lower survival probability.

DNA copy number variations (CNV) are common in cancer development, however, CNV detection approaches that include assessments of small CNVs, for example, due to locally misaligned sister chromatid exchanges, have not been substantially applied. Using such approaches, CNVs have been detected, in the cancer setting, for regulatory elements common to both proliferation and apoptosis effector genes, but no linkage has yet been made to cancer patient clinical data. Thus, we hypothesized that copy number losses, including local copy number losses, of specific apoptosis effector genes would be associated with reduced survival. Both whole genome and whole exome files were processed for validations and consistency. Results indicated lower late-stage survival for multiple myeloma cases representing reduced BAD and CASP3 copies, as well as for lung adenocarcinoma cases representing reduced BAX and CASP3 copies. Results also indicated that neuroblastoma (NBL) cases representing reduced copies of CASP9 and BRCA1 had reduced overall survival probabilities, with the BRCA1 results being particularly notable due to previous reports of BRCA1 inactivating mutations in NBL. Overall, novel approaches to assessing CNVs offers the promise of establishing patient risk stratifications and of identifying single genes or other small spaces in the genome where a CNV may be linked to specific outcomes.