Asimetría de Cancer Hallmarks en tumores mamarios de dieferente lateralidad

CAMPOY, EMANUEL; LAURITO SERGIO; BRANHAM MARIA T; URRUTIA GUILLERMO; MATHISON ANGELA; GAGO FRANCISCO; OROZCO JAVIER; URRUTIA RAÚL; MAYORGA LUIS S; ROQUÉ MARIA

Simposio; Simposio Internacional Programa RAICES, Ganando la Guerra contra el cáncer; 2016

During the last decades it has been established that breast cancer arises through the accumulationof genetic and epigenetic alterations in different cancer related genes. These alterationsconfer the tumor oncogenic abilities, which can be resumed as cancer hallmarks(CH). The purpose of this study was to establish the methylation profile of CpG sites locatedin cancer genes in breast tumors so as to infer their potential impact on 6 CH: i.e. sustainedproliferative signaling, evasion of growth suppressors, resistance to cell death, induction ofangiogenesis, genome instability and invasion and metastasis. For 51 breast carcinomas,MS-MLPA derived-methylation profiles of 81 CpG sites were converted into 6 CH profiles.CH profiles distribution was tested by different statistical methods and correlated with clinical-pathological data. Unsupervised Hierarchical Cluster Analysis revealed that CH profilessegregate in two main groups (bootstrapping 90?100%), which correlate with breast laterality(p = 0.05). For validating these observations, gene expression data was obtained byRealTime-PCR in a different cohort of 25 tumors and converted into CH profiles. This analysesconfirmed the same clustering and a tendency of association with breast laterality(p = 0.15). In silico analyses on gene expression data from TCGA Breast dataset from leftand right breast tumors showed that they differed significantly when data was previouslyconverted into CH profiles (p = 0.033). We show here for the first time, that breast carcinomasarising on different sides of the body present differential cancer traits inferred frommethylation and expression profiles. Our results indicate that by converting methylation orexpression profiles in terms of Cancer Hallmarks, it would allow to uncover veiled associationswith clinical features. These results contribute with a new finding to the better understandingof breast tumor behavior, and can moreover serve as proof of principle for otherbilateral cancers like lung, testes or kidney.