Genome and Targeted Sequencing of Bladder Cancer

One primary bladder cancer and paired peripheral blood sample were subjected to whole genome sequencing on an Illumina HiSeq 2000 platform. This technology was utilized to investigate the genetic basis of a durable remission of metastatic bladder cancer in a patient treated with everolimus, a drug that inhibits the mTOR (mammalian target of rapamycin) signaling pathway. Among the somatic mutations found was a loss-of-function mutation in TSC1 (Tuberous Sclerosis Complex 1), a regulator of mTOR pathway activation. Targeted sequencing using an exon capture and sequencing assay was performed on 13 tumors derived from patients on the same everolimus trial as the index patient and the sequencing data from these tumors is included. TSC1 mutation status was correlated with response to everolimus. The index patient responder tumor and peripheral blood DNA were also subjected to exon capture and sequencing.]]>
All cases were derived from patients on a phase II study of everolimus performed at Memorial Sloan-Kettering Cancer Center (ClinicalTrials.gov number NCT00805129). Patients were analyzed for which adequate tumor and normal tissue was available for sequencing. DNA was extracted from tumor tissue and from peripheral blood or adjacent normal urothelial tissue.]]>