Artículos y presentaciones en Congresos

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Examinando Artículos y presentaciones en Congresos por Autor "Butti, Matías"

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  • Revisión
    Acceso Abierto
    Breast Cancer Biomarker Discovery in the Functional Genomic Age: A Systematic Review of 42 Gene Expression Signatures
    (2010) Abba, Martín Carlos; Lacunza, Ezequiel; Butti, Matías; Aldaz, C. Marcelo
    In this review we provide a systematic analysis of transcriptomic signatures derived from 42 breast cancer gene expression studies, in an effort to identify the most relevant breast cancer biomarkers using a meta-analysis method. Meta-data revealed a set of 117 genes that were the most commonly affected ranging from 12% to 36% of overlap among breast cancer gene expression studies. Data mining analysis of transcripts and protein-protein interactions of these commonly modulated genes indicate three functional modules significantly affected among signatures, one module related with the response to steroid hormone stimulus, and two modules related to the cell cycle. Analysis of a publicly available gene expression data showed that the obtained meta-signature is capable of predicting overall survival (P < 0.0001) and relapse-free survival (P < 0.0001) in patients with early-stage breast carcinomas. In addition, the identified meta-signature improves breast cancer patient stratification independently of traditional prognostic factors in a multivariate Cox proportional-hazards analysis.
  • Artículo
    Acceso Abierto
    A Molecular Portrait of High-Grade Ductal Carcinoma In Situ
    (AACR Publications, 2015) Abba, Martín Carlos; Gong,Ting; Lu, Yue; Lee, Jaeho; Zhong, Yi; Lacunza, Ezequiel; Butti, Matías; Takata, Yoko; Gaddis, Sally; Shen, Jianjun; Estecio, Marcos R.; Sahin, Aysegul A.; Aldaz, C. Marcelo
    Ductal carcinoma in situ (DCIS) is a noninvasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve to invasive cancer whereas others appear not to do so during the life span of the patient. Here, we performed full exome (tumor vs. matching normal), transcriptome, and methylome analysis of 30 pure high-grade DCIS (HG-DCIS) and 10 normal breast epithelial samples. Sixty-two percent of HG-DCIS cases displayed mutations affecting cancer driver genes or potential drivers. Mutations were observed affecting PIK3CA (21% of cases), TP53 (17%), GATA3 (7%), MLL3 (7%) and single cases of mutations affecting CDH1, MAP2K4, TBX3, NF1, ATM, and ARID1A. Significantly, 83% of lesions displayed numerous large chromosomal copy number alterations, suggesting they might precede selection of cancer driver mutations. Integrated pathway-based modeling analysis of RNA-seq data allowed us to identify two DCIS subgroups (DCIS-C1 and DCIS-C2) based on their tumor-intrinsic subtypes, proliferative, immune scores, and in the activity of specific signaling pathways. The more aggressive DCIS-C1 (highly proliferative, basal-like, or ERBB2+) displayed signatures characteristic of activated Treg cells (CD4+/CD25+/FOXP3+) and CTLA4+/CD86+ complexes indicative of a tumor-associated immunosuppressive phenotype. Strikingly, all lesions showed evidence of TP53 pathway inactivation. Similarly, ncRNA and methylation profiles reproduce changes observed postinvasion. Among the most significant findings, we observed upregulation of lncRNA HOTAIR in DCIS-C1 lesions and hypermethylation of HOXA5 and SOX genes. We conclude that most HG-DCIS lesions, in spite of representing a preinvasive stage of tumor progression, displayed molecular profiles indistinguishable from invasive breast cancer.