IDENTIFICATION OF SOMATIC TET2 MUTATIONS BY EXOME SEQUENCING OF METASTATIC PROSTATE TUMORS

Abstract

Prostate cancer is among the most common cancers in men. Metastatic prostate cancer has a high morbidity with no effective long-term cure. In this study, highthroughput exome sequencing was performed on five metastatic prostate tumors from a single patient in order to characterize the genetic variants associated with metastatic prostate cancer. PCR and Sanger sequencing were used to validate the results of the high- throughput sequencing. Sixty-two novel somatic variants were found in this patient, 53 of which were present in all metastatic tumors examined and 9 of which were found in subsets of metastatic tumors. Variants present in the metastatic tumors were also examined in the primary prostate tumor. Genes containing somatic variants were prioritized for further screening in additional metastatic tumors from other patients. Further screening revealed two additional novel somatic alterations and one novel inherited variant in the tumor suppressor gene TET2.