Portal de Periódicos da CAPES

Differential involvement of RASSF2 hypermethylation in breast cancer subtypes and their prognosis

2015; Impact Journals LLC; Volume: 6; Issue: 27 Linguagem: Inglês

10.18632/oncotarget.4062

1949-2553

Noemí Pérez‐Janices, Idoia Blanco‐Luquin, Natalia Torrea, Thérèse Liechtenstein, David Escors, Alicia Córdoba, Francisco Vicente-García, Isabel Jaúregui, Susana De La Cruz, José Juan Illarramendi, Valle Coca, María Berdasco, Grazyna Kochan, Berta Ibáñez, José Miguel Lera, David Guerrero‐Setas,

Cancer-related gene regulation

// Noemi Perez-Janices 1, 2 , Idoia Blanco-Luquin 1, 2, 3 , Natalia Torrea 4 , Therese Liechtenstein 2, 4 , David Escors 2, 4 , Alicia Cordoba 5 , Francisco Vicente-Garcia 6 , Isabel Jauregui 5 , Susana De La Cruz 7 , José Juan Illarramendi 7 , Valle Coca 8 , Maria Berdasco 9 , Grazyna Kochan 4 , Berta Ibañez 10 , José Miguel Lera 6 , David Guerrero-Setas 1 1 Cancer Epigenetics Group, Navarrabiomed-Fundación Miguel Servet (FMS), Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Navarra, Spain 2 Division of Infection and Immunity, Rayne Institute, University College London (UCL), London, United Kingdom 3 Cancer Immunomodulation Group, Navarrabiomed-Fundacion Miguel Servet, IdiSNA, Navarra, Spain 4 Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom 5 Department of Pathology, Complejo Hospitalario de Navarra, Navarra Health Service, Pamplona, Navarra, Spain 6 Department of Surgery, Complejo Hospitalario de Navarra, Navarra Health Service, Navarra, Spain 7 Department of Medical Oncology, Complejo Hospitalario de Navarra, Navarra Health Service, Navarra, Spain 8 Biobank Unit, Navarrabiomed-Fundacion Miguel Servet, IdiSNA, Navarra, Spain 9 Cancer Epigenetics Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain 10 Red de Evaluación en Servicios Sanitarios y Enfermedades Cronicas (REDISSEC), Navarrabiomed-Fundación Miguel Servet, IdiSNA, Navarra, Spain Correspondence to: David Guerrero-Setas, e-mail: dguerres@navarra.es Keywords: breast cancer, DNA methylation, prognosis, RASSF1, RASSF2 Received: January 09, 2015 Accepted: May 22, 2015 Published: June 04, 2015 ABSTRACT Breast cancer is a heterogeneous disease that can be subdivided into clinical, histopathological and molecular subtypes (luminal A-like, luminal B-like/HER2-negative, luminal B-like/HER2-positive, HER2-positive, and triple-negative). The study of new molecular factors is essential to obtain further insights into the mechanisms involved in the tumorigenesis of each tumor subtype. RASSF2 is a gene that is hypermethylated in breast cancer and whose clinical value has not been previously studied. The hypermethylation of RASSF1 and RASSF2 genes was analyzed in 198 breast tumors of different subtypes. The effect of the demethylating agent 5-aza-2′-deoxycytidine in the re-expression of these genes was examined in triple-negative (BT-549), HER2 (SK-BR-3), and luminal cells (T-47D). Different patterns of RASSF2 expression for distinct tumor subtypes were detected by immunohistochemistry. RASSF2 hypermethylation was much more frequent in luminal subtypes than in non-luminal tumors ( p = 0.001). The re-expression of this gene by lentiviral transduction contributed to the differential cell proliferation and response to antineoplastic drugs observed in luminal compared with triple-negative cell lines. RASSF2 hypermethylation is associated with better prognosis in multivariate statistical analysis ( P = 0.039). In conclusion, RASSF2 gene is differently methylated in luminal and non-luminal tumors and is a promising suppressor gene with clinical involvement in breast cancer.