23P - Epigenomic landscape of Breast Cancer in Very Young Women

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Basic Science
Cancer in Young Adults
Breast Cancer
Presenter Sara Oltra Sanchis
Citation Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361
Authors S. Oltra Sanchis1, M.P. Chilet1, M. Martinez2, K. Flower3, E. Alonso2, O. Burgues4, A. Lluch5, J. Flanagan3, G. Ribas1
  • 1Oncología Médica, INCLIVA Instituto de investigación sanitaria, 46010 - Valencia/ES
  • 2Oncología Médica, Hospital Clínico Universitario de Valencia, 46010 - Valencia/ES
  • 3Department Of Surgery And Cancer, Imperial College London, London/GB
  • 4Pathological Anatomy, Hospital Clínico Universitario de Valencia, 46010 - Valencia/ES
  • 5Medical Oncology  , Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES

Abstract

Background

Although less frequent than in older women, breast cancer in very young women (BCVY) (≤35 years old) presents more aggressive and complex biological features. Epigenetic modifications such as miRNA regulation or DNA methylation are reported to play an important role in the onset and progression of cancer. The aim of this work is to identify the epigenetics mechanisms characteristics of BCVY that may be conferring more aggressive features to this group of patients.

Methods

We analysed methylation (Infinium MethylationEPIC BeadChip) from 26 BCVY and 15 samples from women >45 years old. Methylation differences were assessed using Wilcoxon rank sum test. We selected from The Cancer Genome Atlas (TCGA) those genes regulated by significantly different methylated sites and their expression was analysed. MiRNA expression data from TCGA, METABRIC and data previously published from our group was evaluated in a meta-analysis. We then selected those target genes which expression was more affected by miRNA deregulation. Pathway enrichment analysis was performed with most relevant genes from the epigenetic study by Enrichr.

Results

We detected a global hypomethylation profile in BCVY samples and hypermetilation of 502 specific CpG sites exclusive of this group of age. Hypomethylated CpG sites were regulating genes mainly involve in neuronal processes, extracellular matrix and cell communication. Whereas specific hypermethylation was located in genes related to immune system, NOTCH signalling, vesicular trafficking, DNA repair and senescence. MiRNA expression meta-analysis revealed a profile of 22 miRNAs significantly deregulated in BCVY. Pathway enrichment analysis of most affected target genes showed an involvement in neural processes, glucose metabolism, vesicular trafficking, DNA repair, histone and chromatin related proteins, apoptosis, cell cycle, response to DNA damage and senescence.

Conclusions

Our work highlights the presence of epigenomic profile distinctive of BCVY. Both methylation and miRNAs studies points to deregulation of pathways related to neural processes, vesicular trafficking, DNA repair and senescence. All these processes may lead to cancer development and progression, thus genes in these pathways may be potential candidates for further studies.

Clinical trial identification

Legal entity responsible for the study

INCLIVA Research Institute

Funding

None

Disclosure

S. Sanchis: Funded on a FPU predoctoral Fellowship (FPU13/04976) from MINECO, Spanish Government.

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G. Ribas: Funded on a Miquel Servet II contract (CPII14-00013) from CarlosIII Health Institute.

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M.P. Chilet: Funded by private Patients Fundation LeCado. CIBERONC is an initiative of the Carlos III Health Institute.All other authors have declared no conflicts of interest.

Disclosure

S. Sanchis: Funded on a FPU predoctoral Fellowship (FPU13/04976) from MINECO, Spanish Government.

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G. Ribas: Funded on a Miquel Servet II contract (CPII14-00013) from CarlosIII Health Institute.

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M.P. Chilet: Funded by private Patients Fundation LeCado. CIBERONC is an initiative of the Carlos III Health Institute.All other authors have declared no conflicts of interest.

Disclosure

S. Sanchis: Funded on a FPU predoctoral Fellowship (FPU13/04976) from MINECO, Spanish Government.

G. Ribas: Funded on a Miquel Servet II contract (CPII14-00013) from CarlosIII Health Institute.

M.P. Chilet: Funded by private Patients Fundation LeCado. CIBERONC is an initiative of the Carlos III Health Institute.All other authors have declared no conflicts of interest.