Distribution of homopolymeric tracts across the reads.

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

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

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

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

Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study

<div><p>Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a β-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0.006, p = 0.036).When β-diversity was evaluated, the CC samples showed the highest variation within groups (p<0.0006) and the largest distance compared to NCL-HPV negative ones (p<0.00001). The predominant bacteria in women with normal cytology were <i>L</i>. <i>crispatus</i> and <i>L</i>. <i>iners</i>, whereas for SIL, it was <i>Sneathia spp</i>. and for CC, <i>Fusobacterium spp</i>. We found higher median cervical levels of IL-4 and TGF-β1 mRNA in the CST dominated by <i>Fusobacterium spp</i>. These results suggest that the cervical microbiota may be implicated in cervical cancer pathology. Further cohort studies are needed to validate these findings.</p></div

Cervical cytokine mRNA levels normalized to GAPDH, in NCL versus SIL and in NCL versus CC.

<p>(A) IL-4, (B) IL-6, (C) IL-10, (D) TNFα, (E) IFN-γ, (F) TGF-β1. * p value for the Mann-Whitney test (p = 0.04).</p

Distribution of samples in each community state type (CST).

<p>Distribution of samples in each community state type (CST).</p