Variants of uncertain significance (VUS) detected in patients.

1<p>D: deletion; M: missense mutation; S: synonimous mutation; Ts: transition; Tv: transvertion.</p>2<p>B: benign; PD: probably damaging.</p

Distribution of homopolymeric tracts across the reads.

<p>The base number signals are plotted against the sequence reads of the control run.</p

Genealogy of the family 1 carrier of the deleterious mutation c.5114_5117delTAAA in <i>BRCA2</i>.

<p>Index patient is denoted with an arrow. Individuals with cancer are represented with in dark circles or with dark squares; the type of cancer is indicated as follows: Bla: Bladder cancer; Br: Unilateral Breast Cancer; B-Br: Bilateral breast cancer. Current age or known ages of cancer diagnosis and decease are showed. Numbers inside the rhombi indicate quantity of relatives. Asymptomatic carriers are represented with a midline. Unaffected family members confirmed by the predictive molecular testing are shown with a W (wild type).</p

Evaluation of the methodological strategy for the detection of BRCA mutations.

1<p>Number of reads per nucleotide.</p>a<p>Types of mutations: F: frameshift; S: stop.</p

Detection of BRCA deleterious mutations in patients.

1<p>Number of reads per nucleotide.</p>2<p>Types of mutations: F: frameshift; S: stop.</p

Genealogy of the family 15 carrier of the deleterious mutation c.2639_2640delTG in <i>BRCA2</i>.

<p>Individuals with cancer are represented with dark circles or with dark squares; the type of cancer is indicated as follows: Br: unilateral breast cancer; Cr: colorectal cancer; NE: Not especified neoplasia; L: lung cancer; La: laryngeal cancer; Ga: gastric cancer. Index patient is denoted with an arrow. Current age or known ages of cancer diagnosis and decease are showed. Numbers inside the rhombi indicate quantity of first-degree relatives. Asymptomatic carriers are represented with a midline.</p

Clinical features of the patients with <i>BRCA</i> mutations.

a<p>ER  =  estrogen receptor; PR  =  progesterone receptor; HER2/neu  =  human epidermal growth factor receptor 2; Ki-67 =  antigen KI 67.</p

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

<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.

<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

Whole exome sequencing summary statistics.

<p>Whole exome sequencing summary statistics.</p