Abstract 4406
Background
GBAC is an aggressive neoplasm with an abysmal 5-year survival rate and no approved targeted therapies. Incidence of GBAC varies greatly across global geographical regions, with highest reported rates in South and East Asia. We evaluated whether GBAC patients have differential genomic profiles as correlated to ancestry.
Methods
CGP was performed by an adaptor-ligation/hybrid capture-based assay of coding DNA of 315 cancer-related genes and select introns of 28 genes that are frequently involved in genomic rearrangements to detect base substitutions, insertions and deletions, copy number alterations, and rearrangements. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was assessed across 114 homopolymeric loci. Patient ancestry was determined by single nucleotide polymorphism microarray data, ancestry informative markers, and principal component analysis.
Results
The genomic profiles of tumour samples from 881 patients with GBAC were reviewed. Of these samples, 22 (2.50%) were derived from individuals of South Asian ancestry (SAS), 61 (6.92%) from East Asian (EAS) ancestry and the remainder were distributed among African, American, and European ancestry (Others). Age and gender were similar across all three groups, except for an enrichment in SAS male patients (SAS male 68.2%, EAS male 32.7%, Others male 31.2%; p = 0.001). MSI was uncommon in all three groups (0.007% overall) and TMB was low (median 2.6 mut/mb). The most commonly altered genes across all three groups were TP53, CDKN2A/B and SMAD4 (all: 64%, 53%, 17%) while alterations in ERBB2 (23% v 30% v 14%, p = 0.03) and CTNNB1 (14% v 11% v 3%, p = 0.001) were enriched in SAS and EAS populations. Amongst ERBB2 altered cases, amplifications were seen at similar frequencies across all three groups (80% v 72% v 72%), while less than half of all ERBB2 point mutations occurred at the S310 codon (18/67, 27%).
Conclusions
GBAC patients of SAS and EAS ancestry were enriched for ERBB2 and CTNBB1 relative to other ancestries. Follow-up studies are needed to understand the genomic context of this finding, as well as the influence of cancer predisposition genes in the context of ancestry specific oncogenesis.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Foundation Medicine Inc.
Funding
Foundation Medicine Inc.
Disclosure
M. Javle: Research grant / Funding (self): QED Therapeutics; Honoraria (self): Merck & Co; Advisory / Consultancy: EDO Pharma; Advisory / Consultancy: More Health; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Seattle Genetics; Research grant / Funding (self): Meclun; Research grant / Funding (institution): Arqule; Research grant / Funding (institution): Lilly; Advisory / Consultancy: Origimed; Research grant / Funding (self): Novartis. S. Akumalla: Full / Part-time employment: Foundation Medicine; Shareholder / Stockholder / Stock options: Roche. R. Madison: Full / Part-time employment: Foundation Medicine; Shareholder / Stockholder / Stock options: Roche. J. Newburg: Shareholder / Stockholder / Stock options: Foundation Medicine Inc; Shareholder / Stockholder / Stock options: Roche. B.M. Alexander: Leadership role, Full / Part-time employment, Officer / Board of Directors: Foundation Medicine Inc; Shareholder / Stockholder / Stock options: Roche; Advisory / Consultancy, Personal Fees: AbbVie; Advisory / Consultancy, Personal Fees: Schlesinger Associates; Advisory / Consultancy, Personal Fees: Bristol-Myers Squibb; Advisory / Consultancy, Personal Fees: Precision Health Economics; Research grant / Funding (self), grants outside submitted work: Puma Biotechnology; Research grant / Funding (self), grants outside submitted work: Celgene; Research grant / Funding (self), grants outside submitted work: Eli Lily. J. Chung: Full / Part-time employment: Foundation Medicine Inc; Shareholder / Stockholder / Stock options: Roche. V.A. Miller: Full / Part-time employment: Foundation Medicine Inc; Shareholder / Stockholder / Stock options: Roche; Advisory / Consultancy, Scientific Advisory Board: Revolution Medicines. J. Lee: Full / Part-time employment: Foundation Medicine Inc; Shareholder / Stockholder / Stock options: Roche. J.S. Ross: Leadership role, Full / Part-time employment: Foundation Medicine Inc; Shareholder / Stockholder / Stock options: Roche; Officer / Board of Directors: Celcius Therapeutics. A.B. Schrock: Full / Part-time employment: Foundation Medicine Inc; Shareholder / Stockholder / Stock options: Roche. G.M. Frampton: Full / Part-time employment: Foundation Medicine Inc; Shareholder / Stockholder / Stock options: Roche. S.M. Ali: Full / Part-time employment: Foundation Medicine Inc; Shareholder / Stockholder / Stock options: Roche; Advisory / Consultancy, Scientific Advisory Board: Incysus Therapeutics, Inc.; Advisory / Consultancy: Revolution Medicines. All other authors have declared no conflicts of interest.
Resources from the same session
1025 - Liver metastases (LM) from intrahepatic cholangiocarcinoma (iCCA): Outcomes from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry and implications on current American Joint Committee on Cancer (AJCC) staging.
Presenter: Angela Lamarca
Session: Poster Display session 2
Resources:
Abstract
5813 - Is MGMT methylation a new therapeutic target for Biliary Tract Cancer?
Presenter: Monica Niger
Session: Poster Display session 2
Resources:
Abstract
5839 - Biliary Tract Cancers in Portuguese families with BRCA gene mutation: a retrospective study.
Presenter: Patricia Pereira
Session: Poster Display session 2
Resources:
Abstract
4338 - Selection of patients with hepatocellular carcinoma for selective internal radiation therapy based on tumour burden and liver function: a post-hoc analysis of the SARAH trial
Presenter: Daniel Palmer
Session: Poster Display session 2
Resources:
Abstract
1700 - Second-line chemotherapy (SLC) in Patients with Advanced Biliary tract and Gallbladder Cancers (ABGC) Prolongs Survival: A Retrospective Population-based Cohort Study
Presenter: Adnan Zaidi
Session: Poster Display session 2
Resources:
Abstract
5562 - Overall survival of patients with hepatocellular carcinoma receiving sorafenib versus selective internal radiation therapy with predicted dosimetry in the SARAH trial
Presenter: Neil Hawkins
Session: Poster Display session 2
Resources:
Abstract
1838 - Multicenter phase II trial of axitinib monotherapy for advanced biliary tract cancer refractory to gemcitabine-based chemotherapy
Presenter: Naohiro Okano
Session: Poster Display session 2
Resources:
Abstract
3641 - Soluble Programmed Death-ligand 1 indicate poor prognosis in hepatocellular carcinoma patients undergoing transcatheter arterial chemoembolization
Presenter: Xiaolu Ma
Session: Poster Display session 2
Resources:
Abstract
2733 - The Prognostic Nutritional Index (PNI) is an independent predictor of survival in advanced biliary cancers (ABC) receiving first-line chemotherapy (1L).
Presenter: Francesco Caputo
Session: Poster Display session 2
Resources:
Abstract
3773 - Impact of centralisation of national cancer services on patient outcomes for hepatobiliary cancers in Ireland 2000 – 2016
Presenter: David O Reilly
Session: Poster Display session 2
Resources:
Abstract