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
1049 - The Effect Of Multiple Interventions For Women At Risk For Cervical Cancer On Their Health Responsibility, Beliefs Regarding Cervical Cancer, And Having Screening: A Randomized Controlled Experiment
Presenter: Busra Altinel
Session: Poster Display session 2
Resources:
Abstract
1309 - Quantifying the Effects of the Korean National Cancer Screening Program on Cervical Cancer Mortality
Presenter: Nhung Bui
Session: Poster Display session 2
Resources:
Abstract
1346 - Spread of tumor and adverse events after modified radical hysterectomy for FIGO Stage IB1 cervical cancer patients with tumor diameter preoperatively estimated 2 cm or less: Japan Clinical Oncology Group trial (JCOG1101); exploratory analysis before primary analysis.
Presenter: Takahide Arimoto
Session: Poster Display session 2
Resources:
Abstract
5352 - Impact of Combined Interstitial and Intracavitary Brachytherapy in locally advanced Cervical cancer: A Survival and toxicity profile assessment
Presenter: Vibhay Pareek
Session: Poster Display session 2
Resources:
Abstract
2049 - Chemoradiotherapy response prediction model by proteomic expressional profiling in patients with locally advanced cervical cancer
Presenter: Chel Hun Choi
Session: Poster Display session 2
Resources:
Abstract
1923 - Disparities starting adjuvant chemotherapy for locally advanced cervix cancer in the international, academic, randomised, phase 3 OUTBACK trial (ANZGOG 0902, RTOG 1174, NRG 0274)
Presenter: Linda Mileshkin
Session: Poster Display session 2
Resources:
Abstract
3284 - Primary results from CECILIA, a global single-arm phase 2 study evaluating bevacizumab (BEV), carboplatin (C) and paclitaxel (P) for advanced cervical cancer (aCC)
Presenter: Andres Redondo
Session: Poster Display session 2
Resources:
Abstract
843 - Prognostic and clinicopathological significance of PD-L1 in patients with cervical cancer: a meta-analysis
Presenter: Xiaobin Gu
Session: Poster Display session 2
Resources:
Abstract
1020 - Clinical impact of molecular profiling of cervical cancer (CC) patients (pts) in a dedicated Phase I (P1) unit
Presenter: Mariana Scaranti
Session: Poster Display session 2
Resources:
Abstract
872 - Comparative proteomic profiles of cervical cancer and paried paracancerous tissue and the potential effects of DUSP7 over-expression through inhibiting RAS pathway on the biological characteristics of human cervical cancer cell line SIHA
Presenter: Xuan Jiang
Session: Poster Display session 2
Resources:
Abstract