phs001432
A Pilot Study of Rapid Autopsy and Procurement of Tissue in Thoracic Malignancy Cancer Patients to Investigate Tumor Heterogeneity
Integrated proteo-genomics studies to characterize tumor heterogeneity of metastatic lung adenocarcinoma and thymic carcinoma are lacking. We carried out whole exome sequencing, RNA sequencing, copy number estimation and mass spectrometry-based proteomics of 40 tumors from five rapid/warm autopsy patients. We found highly variable mutational heterogeneity that was largely driven by APOBEC-mutagenesis with the expression of APOBEC3B ( Gene ID: 9582) and APOBEC3A_B ( Gene ID: 100913187) due to underlying APOBEC3 region germline variants as the likely mediating mechanism. APOBEC3A_B expression was associated with increased immune tumor microenvironment and CD274 ( Gene ID: 29126) expression while smoking was associated with increased APOBEC-mutagenesis in TP53 ( Gene ID: 7157) mutant tumors with high APOBEC3B expression. Heterogeneity at the level of the transcriptome and proteome occurred in association with copy number heterogeneity, not APOBEC-induced... (for more see dbGaP study page.)