Urinary Bladder Neoplasms study with WXS data on dbGaP (76 participants)

phs003402 — Genomic Tumor Correlates of Clinical Outcomes Following Organ-Sparing    Chemoradiation Therapy for Bladder Cancer

<p>Bladder preservation with trimodality therapy (TMT), consisting of transurethral tumor resection followed by chemoradiation, is an alternative to radical cystectomy for muscle-invasive bladder cancer (MIBC), but molecular determinants of response are poorly understood. Patients with cT2-T4aN0M0 MIBC treated with definitive-intent chemoradiation as part of TMT were retrospectively identified from a single institution between 1986-2015. Pre-treatment Formalin Fixed Paraffin Embedded (FFPE) tumors from 76 MIBC patients were subjected to whole exome sequencing (WES). Our integrated analysis yielded insights into molecular features associated with favorable long-term response to TMT, including alterations in DNA damage response genes. Of these, mutations in <a href="https://www.ncbi.nlm.nih.gov/gene/2068">ERCC2</a>, a DNA helicase in the nucleotide excision repair pathway, were significantly associated with improved long-term outcomes after TMT, particularly in patients who received concurrent cisplatin-based chemotherapy. </p>