Molecular profiling of advanced biliary cancer: lost in translation from bench to bedside

M Doherty, JW Chiu, Mairead Mcnamara, AM Horgan, S Serra, S Kamel-Reid, T Zhang, PL Bedard, D Hedley, NC Dhani, R Jang, JJ Knox

    Research output: Contribution to conferencePoster


    Background: Advanced Biliary Cancer (ABC) is a collection of diseases which carry poor prognosis, and many patients derive limited benefit from chemotherapy. Identification of molecular drivers of ABC may help to predict treatment response and direct development of targeted therapy. Methods: Formalin fixed paraffin embedded (FFPE) tissue form patients with ABC treated at Princess Margaret Cancer Centre was analysed by MassARRAY Sequenom panel (23 genes, 279 mutations), or by next general sequencing (NGS) using Proton or Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons, ≥500x coverage). Clinicopathologic and treatment data were collected from electronic health records. Results: Of 112 tested patients, 16 had insufficient DNA, and 96 had data for analysis: 13 with ampullary cancer (AC), 19 with hilar/distal bile duct (DBD), 43 with gallbladder (GBC), and 21 with intrahepatic (IHC). 13 patients had Sequenom testing, 85 had NGS with Miseq or Proton. 127 mutations were identified in 60 patients, 36 had no mutations detected: 23 in AC, 54 in GBC, 24 in IHC, 26 in DBD. The most frequent mutations were in TP53 (34%) and KRAS (20%). TP53 and SMAD4 mutations appeared most common in GBC, BRAF and KRAS mutations were most common in AC, and IDH1 and FGFR2mutations were seen only in IHC. 14 patients (15%) had a mutation for which targeted treatment could be applied. Conclusions: Profiling of patients with ABC is feasible and can identify some molecular drivers, with different tumour sites demonstrating distinct biological patterns. Only a limited number of patients are shown to have clinically relevant mutations with current NGS techniques, suggesting additional techniques (whole genome/RNA sequencing) may be required to fully characterise these diseases and identify new therapeutic targets.
    Original languageEnglish
    Publication statusPublished - Jan 2016
    EventGI ASCO 2016 - San Francisco
    Duration: 21 Jan 201623 Jan 2016


    ConferenceGI ASCO 2016
    CitySan Francisco


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