13 research outputs found

    p.Gly39val and p.Thr141Ile ABRAXAS mutants have defects in gamma-H2AX formation.

    No full text
    <p>(A) Typical DNA damage foci of ABRAXAS in shABRAXAS (shABX145) MCF7 cells complemented with ABRAXAS-HA-Flag, ABRAXAS-HA-Flag pThr141Ile, or ABRAXAS-HA-Flag pGly39Val. The anti-Flag antibody was used to monitor ABRAXAS foci formation (green), anti-gamma-H2AX (red) and the merge picture is depicted. In blue, DAPI staining. (B) Quantification of gamma-H2AX foci formation in MCF7 cells after neocarzinostatin treatment and release. P-values were obtained with a Wilcoxon’s Test with N = 100 cells from four independent experiments.</p

    Revealing the Molecular Portrait of Triple Negative Breast Tumors in an Understudied Population through Omics Analysis of Formalin-Fixed and Paraffin-Embedded Tissues

    No full text
    <div><p>Triple negative breast cancer (TNBC), defined by the lack of expression of the estrogen receptor, progesterone receptor and human epidermal receptor 2, is an aggressive form of breast cancer that is more prevalent in certain populations, in particular in low- and middle-income regions. The detailed molecular features of TNBC in these regions remain unexplored as samples are mostly accessible as formalin-fixed paraffin embedded (FFPE) archived tissues, a challenging material for advanced genomic and transcriptomic studies. Using dedicated reagents and analysis pipelines, we performed whole exome sequencing and miRNA and mRNA profiling of 12 FFPE tumor tissues collected from pathological archives in Mexico. Sequencing analyses of the tumor tissues and their blood pairs identified <i>TP53</i> and <i>RB1</i> genes as the most frequently mutated genes, with a somatic mutation load of 1.7 mutations/exome Mb on average. Transcriptional analyses revealed an overexpression of growth-promoting signals (EGFR, PDGFR, VEGF, PIK3CA, FOXM1), a repression of cell cycle control pathways (TP53, RB1), a deregulation of DNA-repair pathways, and alterations in epigenetic modifiers through miRNA:mRNA network de-regulation. The molecular programs identified were typical of those described in basal-like tumors in other populations. This work demonstrates the feasibility of using archived clinical samples for advanced integrated genomics analyses. It thus opens up opportunities for investigating molecular features of tumors from regions where only FFPE tissues are available, allowing retrospective studies on the search for treatment strategies or on the exploration of the geographic diversity of breast cancer.</p></div

    PAM50 classification of TNBC samples.

    No full text
    <p>The hierarchically-clustered normalized expression values of the PAM50 classifier genes is shown for the 12 triple negative breast cancers (TNBCs) analyzed and the five centroids. The samples were classified according to their correlation with the PAM50 centroids. Red and blue boxes represent overexpressed and down-regulated genes, respectively.</p
    corecore