Intratumor heterogeneity index of breast carcinomas based on DNA methyla􀆟on profiles

CAMPOY, EMANUEL MARTIN; BRANHAM, MARÍA T.; MAYORGA, LUIS; ROQUÉ, MARÍA

Mar del Plata

Congreso; LXIII Reunión Científica Anual de la SAIC; 2018

Sociedad Argentina de Investigación Clínica

BackgroundCancer cells evolve and constitute heterogeneous populations that uctuate in space and time and are subjected to selection generating intratumor heterogeneity. This phenomenon is determined by theacquisition of genetic/epigenetic alterations and their selection over time which has clinical implications on drug resistance.MethodsDNA extracted from dierent tumor cell populations (breast carcinomas, cancer cell lines and cellular sub-clones) were analyzed by MS-MLPA. Methylation proles were used to generate a heterogeneityindex to quantify the magnitude of epigenetic heterogeneity in these populations.ResultsThe study of methylation proles of 23 fresh breast carcinomas revealed heterogeneous allele populations in these tumor pieces. With the purpose to measure the magnitude of epigenetic heterogeneity,we develop a heterogeneity index (HI) based on methylation information and observed that all tumors present their own heterogeneity level. Applying the index calculation in pure cancer cell populationssuch as cancer cell lines (MDA-MB 231, MCF-7, T47D, HeLa and K-562), we also observed epigenetic heterogeneity. In addition, we detected that sub-clones obtained from MDA-MB 231 cancer cell line divergedfrom the initial population over time and generated their own new heterogeneity without selective pressure. Using epigenetic information derived from TCGA tumors, we determined that the heterogeneityindex correlated with prognostic and predictive factors like tumor size (p=0.0088), number of aected axillary nodes (p=0.007), estrogen receptor expression (p