High-Throughput Sequencing of Germline and Tumor From Men with Early-Onset Metastatic Prostate Cancer
Technical Report,30 Sep 2013,29 Sep 2016
Regents of the University of Michigan Ann Arbor United States
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This research project focused on genetic analysis of a rare subset of prostate cancer cases men presenting with metastatic prostate cancer at a young age before age 60 years. Whole exome sequencing identified a panel of germline variants that have biological as well as genetic evidence suggesting that they may be related to inherited susceptibility of early-onset aggressive prostate cancer. Comprehensive tumor genome andor transcriptome sequencing of tumors from these patients identified an increased frequency of TP53 mutations compared to previously-reported unselected populations suggesting that this may be used as a prognostic marker for aggressive disease in the future. Finally, analysis of paired samples from unique patients confirmed the role of transdifferentiation as the mechanism for the development of NePC as well as CTNNB1 and PIK3CA mutations in adaptive resistance to treatment.
- Medicine and Medical Research