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Asymmetric Cancer Hallmarks in Breast Tumors on Different Sides of the Body. PLoS One 2016;11(7):e0157416 PMID: 27383829 PMCID: PMC4934783

Pubmed ID

27383829

DOI

10.1371/journal.pone.0157416

Abstract

During the last decades it has been established that breast cancer arises through the accumulation of genetic and epigenetic alterations in different cancer related genes. These alterations confer 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 located in cancer genes in breast tumors so as to infer their potential impact on 6 CH: i.e. sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, induction of angiogenesis, 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 profiles segregate in two main groups (bootstrapping 90-100%), which correlate with breast laterality (p = 0.05). For validating these observations, gene expression data was obtained by RealTime-PCR in a different cohort of 25 tumors and converted into CH profiles. This analyses confirmed 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 left and right breast tumors showed that they differed significantly when data was previously converted into CH profiles (p = 0.033). We show here for the first time, that breast carcinomas arising on different sides of the body present differential cancer traits inferred from methylation and expression profiles. Our results indicate that by converting methylation or expression profiles in terms of Cancer Hallmarks, it would allow to uncover veiled associations with clinical features. These results contribute with a new finding to the better understanding of breast tumor behavior, and can moreover serve as proof of principle for other bilateral cancers like lung, testes or kidney.

Author List

Campoy EM, Laurito SR, Branham MT, Urrutia G, Mathison A, Gago F, Orozco J, Urrutia R, Mayorga LS, Roqué M

Authors

Angela Mathison PhD Assistant Professor in the Surgery department at Medical College of Wisconsin
Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin




Scopus

2-s2.0-84978159641   2 Citations

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Breast Neoplasms
Carcinoma
Cohort Studies
CpG Islands
DNA Methylation
Epigenesis, Genetic
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Middle Aged
jenkins-FCD Prod-310 bff9d975ec7f2d302586822146c2801dd4449aad