Aberrant methylation of WT1: a potential epigenetic marker for invasive ductal breast carcinomas

LAURITO S.R.; MARZESE D.M.; URRUTIA G.; GAGO F.E.; OROZCO J.I.; TELLO O.M.; VARGAS ROIG L.M.; ROQUÉ M.

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2012

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

The methylation of cancer related gene promoters is a common event during tumorigenic process. The identification of oncologic methylation markers may contribute as a tool for early detection, disease follow-up and treatment response. Previous studies of our group showed that a CpG island at position -411pb of WT1 gene, was frequently methylated in invasive ductal breast carcinomas (IDCs). In the present work, we included 96 IDCs, 30 normal breast tissues obtained from surgical margins and 25 sentinel lymph nodes, and analyzed the methylation status of WT1, and 27 more CpG islands of different cancer related genes, by MS-MLPA assay. Our results revealed that the methylation of WT1 is the most frequent alteration detected in IDCs (92.7%), and that it allows discriminating between tumor and normal breast tissue (p<0.0001). Besides, we could establish that the aberrant methylation is acquired since early tumor stages (Stage1 and Stage2A) and that is conserved in affected lymph nodes (24/25 sentinel lymph nodes presented methylated WT1). Real Time PCR confirmed this methylation silences WT1. Our results allow postulating WT1 as an epigenetic marker of IDCs. Besides, we postulate that this frequent feature of IDCs from our population could be an indicator to drug sensitivity, e.g.TNF-Related Apoptosis-Inducing Ligand (TRAIL), currently under study for leukemias which do not express WT1.