Acceleration in the DNA methylation age in breast cancer tumours from very young women

Autores de INCLIVA

• Sara Oltra Sanchis

  Autor

• Maria Del Carmen Peña Chilet

  Autor

• 

  Maria Teresa Martinez Martinez

  Autor

• Elisa Alonso Yuste

  Autor

• Octavio Burgues Gasion

  Autor

• 

  Ana Lluch Hernández

  Autor

Participantes ajenos a INCLIVA

• Flower, K
• Flanagan, JM
• Ribas, G

Grupos y Plataformas de I+D+i

• Grupo de Investigación en Biología en Cáncer de mama

  

  Leading Researcher

  Pilar Eroles Asensio

• Grupo de Investigación en Cáncer Colorrectal y Nuevos Desarrollos Terapéuticos en Tumores Sólidos

  

  Leading Researcher

  Andrés Cervantes Ruiperez

Abstract

Breast cancer in very young women (<= 35 years; BCVY) presents more aggressive and complex biological features than their older counterparts (BCO). Our aim was to evaluate methylation differences between BCVY and BCO and their DNA epigenetic age. EPIC and 450k Illumina methylation arrays were used in 67 breast cancer tumours, including 32 from BCVY, for methylation study and additionally we analysed their epigenetic age. We identified 2 219 CpG sites differently-methylated in BCVY vs. BCO (FDR < 0.05; beta-value difference +/- 0.1). The signature showed a general hypomethylation profile with a selective small hypermethylation profile located in open-sea regions in BCVY against BCO and normal tissue. Strikingly, BCVY presented a significant increased epigenetic age-acceleration compared with older women. The affected genes were enriched for pathways in neuronal-system pathways, cell communication, and matrix organisation. Validation in an independent sample highlighted consistent higher expression of HOXD9, and PCDH10 genes in BCVY. Regions implicated in the hypermethylation profile were involved in Notch signalling pathways, the immune system or DNA repair. We further validated HDAC5 expression in BCVY. We have identified a DNA methylation signature that is specific to BCVY and have shown that epigenetic age-acceleration is increased in BCVY.

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.