Feasibility and clinical utility of endoscopic ultrasound guided biopsy of pancreatic cancer for next-generation molecular profiling
| Autor: | John Marshall, Dario Beraldi, Susie Cooke, Colin J. McKay, Nigel B. Jamieson, Fraser Duthie, Rosanna Upstill-Goddard, Andrew V. Biankin, C. Ross Carter, Euan J. Dickson, David K. Chang, Stephen R Knight, Stephan Dreyer, Lisa Evers |
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| Rok vydání: | 2019 |
| Předmět: |
Endoscopic ultrasound
Oncology Image-Guided Biopsy medicine.medical_specialty medicine.disease_cause DNA sequencing 03 medical and health sciences 0302 clinical medicine CDKN2A Pancreatic cancer Internal medicine Biopsy medicine GNAS complex locus Biomarkers Tumor Humans Molecular Targeted Therapy Endoscopic Ultrasound-Guided Fine Needle Aspiration medicine.diagnostic_test biology Molecular pathology business.industry Patient Selection High-Throughput Nucleotide Sequencing General Medicine medicine.disease Prognosis digestive system diseases Pancreatic Neoplasms 030220 oncology & carcinogenesis biology.protein Feasibility Studies 030211 gastroenterology & hepatology KRAS business |
| Zdroj: | Chinese clinical oncology. 8(2) |
| ISSN: | 2304-3873 2304-3865 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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