Pan-Cancer Analysis of Genomic Sequencing among the Elderly

Publication date: Available online 7 January 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Daniel R. Wahl, Paul Nguyen, Maria Santiago, Kasra Yousefi, Elai Davicioni, Dean A. Shumway, Corey Speers, Rohit Mehra, Felix Y. Feng, Joseph R. Osborne, Daniel E. Spratt
IntroductionWe hypothesized that elderly patients may have age-specific genetic abnormalities yet be underrepresented in currently available sequencing repositories, which could limit the impact of sequencing efforts for this population.Methods and MaterialsLeveraging The Cancer Genome Atlas (TCGA) data-portal, 9 tumor types were analyzed. Frequency distribution of cancer by age was determined and compared to Surveillance, Epidemiology, and End Results (SEER) data. Using the estimated median somatic mutational frequency of each tumor type, the samples needed beyond TCGA to detect a 10% mutational frequency were calculated. Micro-array data from a separate prospective cohort were obtained from primary prostatectomy samples to determine if elderly-specific transcriptomic alterations could be identified.ResultsOf the 5,236 TCGA samples, 73% were in patients younger than age 70. Comparing the distribution of TCGA samples by age to SEER data, patients <70 were well represented across most tumor types, but patients 80-99 years old were underrepresented in all cancers (median TCGA underrepresentation of 167%). All cancers (except colorectal) contained enough samples to detect a 10% mutational frequency in patients <60 years old. In contrast, no cancer type had enough samples for which a 10% mutational frequency could be detected in patients ≥80 years old. To further interrogate whether elderly patients with cancer were likely to harbor age-specific molecular abnormalities, we accessed transcriptomic data from a separate, larger database of over 2,000 prostate cancer samples. This analysis revealed significant differences in the expression of 10 genes in patients ≥70 years old compared to those younger than 70, of which 7 are involved in androgen signaling and/or DNA repair.ConclusionsElderly patients are underrepresented in genomic sequencing studies. Our data suggest the presence of elderly-specific molecular alterations. Further dedicated efforts to understand the biology of cancer among the elderly will be important moving forward.



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