Abstract 254P
Background
HGSOC and BLBC are aggressive cancers that share aetiology, co-occur frequently and share molecular signatures including cyclin E1 deregulation. In HGSOC, we have described two cyclin E1 high groups, with and without associated gene amplification. We aimed to determine which subsets of these disease have the greatest similarity in terms of cyclin E1 as a biomarkers of response with the ultimate aim of groping similar subsets in the future for therapeutic purposes.
Methods
Using automated tissue based assays, we assessed the expression and the amplification status of cyclin E1 in a cohort enriched for familial cancer mutations against each of the expression of cyclin E1 degradation associated proteins, i.e., FBXW7 and USP28, BRCA status and clinical outcome and in comparison with cyclin E1 high subsets of HGSOC.
Results
For BLBC cyclin E1 overexpression but not CCNE1 amplification was found to be prognostic for overall survival. By comparison, both cyclin E1 expression and CCNE1 gene amplification are prognostic for HGSOC, which we establish with a meta-analysis of existing studies. We examined the nature of CCNE1 amplification to find that HGSOC has an enhanced degree of amplification of CCNE1 with 5.6x copies compared to 3.9x CCNE1 copies in BLBC, and this was associated with widely different expression of cyclin E1 protein. We find that BLBC cancers, with or without CCNE1 amplification, have similarities in dysregulation of regulators of cyclin E1 protein stability and those shared more features with the non-amplified cyclin E1 high HGSOC subset. Since cyclin E1 is only expressed at high levels in HGSOC and not BLBC, we examined the consequence of very high cyclin E1 expression in a BLBC cell line, MDA-MB-468. Moderate overexpression of cyclin E1 showed increased survival upon treatment with Paclitaxel, however very high expression of cyclin E1 gave less survival benefit.
Conclusions
We conclude that cyclin E1 high BLBC shared features with the non-amplified cyclin E1 high subset, high cyclin E1 expression associated with CCNE1 amplification gives rise to a unique phenotype in HGSOC, but otherwise the high expression of cyclin E1 protein may be a similar prognostic marker for BLBC and HGSOC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Ventana Medical System.
D. Aziz: Research grant / Funding (self), provided reagents and technical support: Ventana Medical System. P.M. Waring: Research grant / Funding (institution), Full / Part-time employment, provided reagents and technical support, worked for about 10 months for ventana during the project: Ventana Medical System. All other authors have declared no conflicts of interest.
Resources from the same session
371P - Clinical utility of Encyclopedic tumour analysis to treat patients advanced refractory head and neck cancers
Presenter: Rajnish Nagarkar
Session: Poster display session
Resources:
Abstract
372P - Real-world fusion landscape in advanced Chinese pancreatic cancer using next generation sequecing: A multicenter study
Presenter: Yiyu Shen
Session: Poster display session
Resources:
Abstract
373P - Molecular profiling of non-small cell lung cancer (NSCLC) in Asia with targeted next-generation sequencing (NGS): Interim analysis of a co-operative group study (ATORG-001)
Presenter: Aaron Tan
Session: Poster display session
Resources:
Abstract
374P - Circulating tumour DNA (ctDNA) identifies actionable genetic alterations in Middle Eastern and Asian (MEA) patients diagnosed with carcinoma of unknown primary (CUP)
Presenter: Nir Peled
Session: Poster display session
Resources:
Abstract
375P - Whole-exome sequencing of tumour-only samples reveals the association between somatic alterations and clinical features in pancreatic cancer
Presenter: Huixin Lin
Session: Poster display session
Resources:
Abstract
376P - Adoption of molecular testing in breast cancer in a tertiary care center in a developing country
Presenter: Prasanta Dash
Session: Poster display session
Resources:
Abstract
377P - NGS in advanced NSCLC in a developing country: Ready for prime time?
Presenter: Amrith B P
Session: Poster display session
Resources:
Abstract
378P - Germline BRCA1/2 testing: Trend in Tan Tock Seng Hospital Singapore
Presenter: Chia Wei Lim
Session: Poster display session
Resources:
Abstract
379P - Study of germline mutations in high risk cancer patients from a tertiary care center in India
Presenter: Padmaj Kulkarni
Session: Poster display session
Resources:
Abstract
380P - Ventricular–Subventricular zone involvement: A predictive factor for survival in glioblastoma
Presenter: Vibhay Pareek
Session: Poster display session
Resources:
Abstract