IP: Dr. Jacinto García

Resumen del proyecto: The response to preoperative radiochemotherapy (RQT) in rectal cancer is highly variable and not the factors on which depends the answer, finding three groups of patients are known: patients with complete response (5-25%), partial (40 -60%) and those who show a complete resistance to preoperative RQT (20-30%). In the genesis of this resistance could play a major role genetic heterogeneity of tumor associated with the existence of different tumor cell subpopulations that may present different degrees of resistance. Our hypothesis is based on rectal tumors have different chromosomal abnormalities, chromosomal abnormalities such coexist within the same tumor in different clones of neoplastic cells, reflecting a high genetic heterogeneity intratumoral level; some of these clones of tumor cells may be responsible for resistance RQT. Therefore, the identification of chromosomal alterations in paired samples pre and post RQT, could help to identify genetic abnormalities associated with increased sensitivity or resistance to preoperative treatment in these patients. In this project we propose to describe genetic profiles and patterns of clonal evolution of rectal cancer by analyzing a total of 60 paired samples of pre and post treatment tumor with RQT using multiple labels with technique of fluorescence in situ hybridization on interphase nuclei (iFish) with in order to determine whether neoplastic clones detected in the pre-RQT sample are present in the post-treatment sample. Subsequently, using high density arrays of single nucleotide polymorphisms, a technique that provides greater resolution defining the limits of chromosomal alterations found, we analyze the variations in the number of copies of DNA between pre- and post-RQT samples . Our goal focuses on establishing the potential impact of genetic heterogeneity intratumoral level in response to treatment by analyzing the effect of this on the proliferation and cell death by apoptosis at the level of the different cell subpopulations coexist in the same tumor.

Entidad financiadora: Consejería de Sanidad de la Junta de Castilla y León