Asymmetric Cancer Hallmarks in Breast Tumors on Different Sides of the Body.

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

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2016

1932-6203

During the last decades it has been establishedthat breast cancer arises through the accumulation of genetic and epigeneticalterations in different cancer related genes. These alterations confer thetumor oncogenic abilities, which can be resumed as cancer hallmarks (CH). Thepurpose of this study was to establish the methylation profile of CpG siteslocated in cancer genes in breast tumors so as to infer their potential impacton 6 CH: i.e. sustained proliferative signaling, evasion of growth suppressors,resistance to cell death, induction of angiogenesis, genome instability andinvasion and metastasis. For 51 breast carcinomas, MS-MLPA derived-methylationprofiles of 81 CpG sites were converted into 6 CH profiles. CH profilesdistribution was tested by different statistical methods and correlated withclinical-pathological data. Unsupervised Hierarchical Cluster Analysis revealedthat CH profiles segregate in two main groups (bootstrapping 90-100%), whichcorrelate with breast laterality (p=0.05). For validating these observations,gene expression data was obtained by RealTime-PCR in a different cohort of 25tumors and converted into CH profiles. This analyses confirmed the same clusteringand a tendency of association with breast laterality (p=0.15). In silico analyses on gene expressiondata from TCGA Breast dataset from left and right breast tumors showed thatthey differed significantly when data was previously converted into CH profiles(p=0.033). We show here for the first time, that breast carcinomas arising ondifferent sides of the body present differential cancer traits inferred frommethylation and expression profiles. Our results indicate that by convertingmethylation or expression profiles in terms of Cancer Hallmarks, it would allowto uncover veiled associations with clinical features. These results contributewith a new finding to the better understanding of breast tumor behavior, andcan moreover serve as proof of principle for other bilateral cancers like lung,testes or kidney.