Feasibility and clinical utility of endoscopic ultrasound guided biopsy of pancreatic cancer for next-generation molecular profiling.

Dreyer, S. B. et al. (2019) Feasibility and clinical utility of endoscopic ultrasound guided biopsy of pancreatic cancer for next-generation molecular profiling. Chinese Clinical Oncology, 8(2), 16. (doi: 10.21037/cco.2019.04.06) (PMID:31070037)

Abstract

Next-generation sequencing is enabling molecularly guided therapy for many cancer types, yet failure rates remain relatively high in pancreatic cancer (PC). The aim of this study is to investigate the feasibility of genomic profiling using endoscopic ultrasound (EUS) biopsy samples to facilitate personalised therapy for PC. Ninty-five patients underwent additional research biopsies at the time of diagnostic EUS. Diagnostic formalin-fixed (FFPE) and fresh frozen EUS samples underwent DNA extraction, quantification and targeted gene sequencing. Whole genome (WGS) and RNA sequencing was performed as proof of concept. Only 2 patients (2%) with a diagnosis of PC had insufficient material for targeted sequencing in both FFPE and frozen specimens. Targeted panel sequencing (n=54) revealed mutations in PC genes (KRAS, GNAS, TP53, CDKN2A, SMAD4) in patients with histological evidence of PC, including potentially actionable mutations (BRCA1, BRCA2, ATM, BRAF). WGS (n=5) of EUS samples revealed mutational signatures that are potential biomarkers of therapeutic responsiveness. RNA sequencing (n=35) segregated patients into clinically relevant molecular subtypes based on transcriptome. Integrated multi-omic analysis of PC using standard EUS guided biopsies offers clinical utility to guide personalized therapy and study the molecular pathology in all patients with PC.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jamieson, Professor Nigel and Dreyer, Dr Stephan and Cooke, Dr Susie and Evers, Ms Lisa and Biankin, Professor Andrew and Duthie, Dr Fraser and Beraldi, Dr Dario and McKay, Mr Colin and Marshall, Mr John
• Authors: Dreyer, S. B., Jamieson, N. B., Evers, L., Duthie, F., Cooke, S., Marshall, J., Beraldi, D., Knight, S., Upstill-Goddard, R., Dickson, E. J., Carter, C. R., McKay, C. J., Biankin, A. V., and Chang, D. K.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Chinese Clinical Oncology
• Publisher: AME Publishing Company
• ISSN: 2304-3865
• ISSN (Online): 2304-3873
• Copyright Holders: Copyright © 2019 Chinese Clinical Oncology
• First Published: First published in Chinese Clinical Oncology 8(2):16
• Publisher Policy: Reproduced with the permission of the publisher