Abstract 5203
Background
Breast cancers display substantial inter/intra-tumor heterogeneity. While numerous fusion genes have been identified, most are found to be subclonal, passenger alterations. To discover fusion genes which drive tumor progression and metastasis, we performed RNA-sequencing of matched primary and metastatic breast cancer samples.
Methods
RNA-sequencing was performed from sixteen patients matched primary-recurrent tumor tissue and RNA-sequencing data was successfully achieved from sixteen primary tumors and eight recurrent tumors. DeFuse program was used to identify fusion transcripts (FT).
Results
Among the sixteen patients, six were hormone receptor positive, three were HER2 positive and seven were triple negative tumors. Three cases displayed loco-regional recurrence only and other patients had distant metastases. Overall, 516 fusion transcripts were identified. Mean numbers of fusions in primary and recurred tumors were 28 and 14.6 FTs per sample. Numbers of fusions were greater in two cases with BRCA1 pathogenic germline mutations while no significant differences were observed across subtypes. Novel inter-chromosomal fusion transcript, BCL2-ESR1, CSMD1-ESR1 and HPGDS-ESR1 were found in one hormone receptor positive patient’s metastasis and/or primary tumor. All fusions resulted in preservation of the DNA-binding domain and ligand-binding domain (exon4-10) of the ESR1 gene, with high ESR1 FPKM expression value. Fusions of ERBB2-, MALAT1- and CDK6- genes were found. Among the identified FTs, three cases harbored a previously reported recurrent fusion transcript EEF1DP3-FRY.
Conclusions
RNA sequencing revealed numerous fusion transcripts. Among them we found novel fusions including ESR1 fusions which need further validation and functional annotation to confirm their role in tumor progression and metastasis.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Asan Medical Center.
Disclosure
All 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