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
3716 - Prognostic factors for predicting early recurrence within the first year of surgery in pancreatic ductal adenocarcinoma
Presenter: Naru Kim
Session: Poster Display session 2
Resources:
Abstract
3947 - Integrated population pharmacokinetic modelling of liposomal irinotecan in patients with various tumour types, including untreated metastatic pancreatic cancer (mPC)
Presenter: Teresa Macarulla
Session: Poster Display session 2
Resources:
Abstract
2880 - Expression of long noncoding RNA and clinical outcomes of pancreatic cancer patients who received adjuvant chemotherapy by S-1 or GEM after curative resection.
Presenter: Mariko Kamiya
Session: Poster Display session 2
Resources:
Abstract
5029 - POLO: Time to treatment discontinuation and subsequent therapies following maintenance olaparib for patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC)
Presenter: Eric Van Cutsem
Session: Poster Display session 2
Resources:
Abstract
4730 - Diagnostic Value of Digital Multiplexed Detection of Single Nucleotide Variants in Pancreatic Cancer Specimens Collected by Endoscopic Ultrasound Fine-Needle Aspiration
Presenter: Irina Cazacu
Session: Poster Display session 2
Resources:
Abstract
3303 - Phase I/II study of LDE225 in combination with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer
Presenter: Esther Pijnappel
Session: Poster Display session 2
Resources:
Abstract
2009 - Efficacy of platinum-containing chemotherapy and prognosis of pancreatic cancer patients with homologous recombination deficiency: meta-analysis of published clinical studies
Presenter: Elizeveta Polyanskaya
Session: Poster Display session 2
Resources:
Abstract
2164 - Plasmatic CXCL8 is a marker for TGFß-activated kinase 1 (TAK1) activation which may predict resistance to nanoliposomal irinotecan (nal-IRI) in gemcitabine-refractory pancreatic cancer (PC) patients
Presenter: Valeria Merz
Session: Poster Display session 2
Resources:
Abstract
2529 - A protein level signature of four selected genes associated with survival outcomes of patients with pancreatic ductal adenocarcinoma
Presenter: Jie Hua
Session: Poster Display session 2
Resources:
Abstract
4947 - Pre-treatment serum 25-hydroxyvitamin D levels and survival in a Danish cohort of patients with pancreatic cancer
Presenter: Louise Rasmussen
Session: Poster Display session 2
Resources:
Abstract