Sun exposure and PDZK1 genotype modulate PDZK1 gene expression in normal skin

Human skin pigmentation results from the enzymatically controlled synthesis of melanin pigments in specialized organelles (melano‐somes) produced within epidermal melanocytes, followed by their transfer to neighboring keratinocytes and their distribution through‐out the epidermis.1 Constitutive skin pigmentation seems to be mostly genetically determined,2 being altered by numerous intrinsic and extrinsic factors affecting the epidermal melanin unit

Differential microRNA expression in breast cancer patients aged 35 years or younger

Genetic 3’UTR variation is associated with human pigmentation characteristics and sensitivity to sunlight

Sunlight exposure induces signalling pathways leading to the activation of melanin synthesis and tanning response. MicroRNAs (miRNAs) can regulate the expression of genes involved in pigmentation pathways by binding to the complementary sequence in their 3'untranslated regions (3'UTRs). Therefore, 3'UTR SNPs are predicted to modify the ability of miRNAs to target genes, resulting in differential gene expression. In this study, we investigated the role in pigmentation and sun-sensitivity traits, as well as in melanoma susceptibility, of 38 different 3'UTR SNPs from 38 pigmentation-related genes. A total of 869 individuals of Spanish origin (526 melanoma cases and 343 controls) were analysed.…

Primary results of the first nationwide molecular screening program in Spain for patients with advanced breast cancer (AGATA SOLTI-1301 study)

Assessing molecular subtypes of gastric cancer: microsatellite unstable and Epstein-Barr virus subtypes. Methods for detection and clinical and pathological implications.

Background The molecular classification of gastric cancer recognises two subtypes prone to immune checkpoint blockade: the microsatellite unstable and the Epstein-Barr virus (EBV)-related tumours. We aim to assess the concordance between immunohistochemistry and PCR for microsatellite status evaluation, and explore the value of microsatellite instability (MSI) and EBV as predictive survival factors. Material and methods We collected 246 consecutively diagnosed gastric cancer cases in all stages and evaluated the microsatellite status using immunohistochemistry for mismatched repair (MMR) proteins and PCR. EBV expression was studied through in situ hybridisation. Results Forty-five (18%) cas…

Low miR200c expression in tumor budding of invasive front predicts worse survival in patients with localized colon cancer and is related to PD-L1 overexpression

At the histological level, tumor budding in colon cancer is the result of cells undergoing at least partial epithelial-to-mesenchymal transition. The microRNA 200 family is an important epigenetic driver of this process, mainly by downregulating zinc-finger E-box binding homeobox (ZEB) and transforming growth factor beta (TGF-β) expression. We retrospectively explored the expression of the miR200 family, and ZEB1 and ZEB2, and their relationship with immune resistance mediated through PD-L1 overexpression. For this purpose, we analyzed a series of 125 colon cancer cases and took samples from two different tumor sites: the area of tumor budding at the invasive front and from the tumor center…

Incidence of oncogenes in PI3K/AKT and MAPK signaling pathways in breast cancer

Additional file 1: of Sex-specific genetic effects associated with pigmentation, sensitivity to sunlight, and melanoma in a population of Spanish origin

This contains Tables S1–S3 and Figures S1–S2. Table S1. List of 363 successfully genotyped SNPs, Minor allele frequencies for all samples, males and females, and HWE P value. Table S2. List of SNPs associated with pigmentation traits in females and males. Table S3. List of SNPs associated with sun response traits in females and males. Figure S1. Comparison of minor allele frequencies, female versus male individuals. Figure S2. A selection of genetic factors affecting pigmentation and sun sensitivity in humans. (PDF 417 kb)

MicroRNA Profile in Response to Doxorubicin Treatment in Breast Cancer

UNLABELLED Chemotherapy treatment is the standard in triple negative breast cancers, a cancer subgroup which lacks a specific target. The mechanisms leading to the response, as well as any markers that allow the differentiation between responder and non-responder groups prior to treatment are unknown. In parallel, miRNAs can act as oncogenes or tumor suppressors and there is evidence of their involvement in promoting resistance to anticancer drugs. Therefore we hypothesized that changes in miRNA expression after doxorubicin treatment may also be relevant in treatment response. OBJECTIVE To study miRNAs that are differentially expressed in response to doxorubicin treatment. METHODS One lumin…

MassARRAY determination of somatic oncogenic mutations in solid tumors: Moving forward to personalized medicine.

This article will review the impact of the recently developed MassARRAY technology on our understanding of cancer biology and treatment. Analysis of somatic mutations is a useful tool in selecting personalized therapy, and for predicting the outcome of many solid tumors. Here, we review the literature on the application of MassARRAY technology (Sequenom Hamburg, Germany) to determine the mutation profile of solid tumors from patients. We summarize the use of commercially available panels of mutations - such as OncoCarta™ or other combinations - and their concordance with results obtained by using other technologies, such as next generation sequencing.

HDAC5 Inhibitors as a Potential Treatment in Breast Cancer Affecting Very Young Women

Background: Breast cancer in very young women (BCVY) defined as &lt

Global transcriptome deregulation of breast cancer in very young women samples

Determination of somatic oncogenic mutations linked to target-based therapies using MassARRAY technology

Somatic mutation analysis represents a useful tool in selecting personalized therapy. The aim of our study was to determine the presence of common genetic events affecting actionable oncogenes using a MassARRAY technology in patients with advanced solid tumors who were potential candidates for target-based therapies. The analysis of 238 mutations across 19 oncogenes was performed in 197 formalin-fixed paraffin-embedded samples of different tumors using the OncoCarta Panel v1.0 (Sequenom Hamburg, Germany). Of the 197 specimens, 97 (49.2%) presented at least one mutation. Forty-nine different oncogenic mutations in 16 genes were detected. Mutations in KRAS and PIK3CA were detected in 40/97 (4…

Deregulation of ARID1A, CDH1, cMET and PIK3CA and target-related microRNA expression in gastric cancer.

Genetic and epigenetic alterations play an important role in gastric cancer (GC) pathogenesis. Aberrations of the phosphatidylinositol-3-kinase signaling pathway are well described. However, emerging genes have been described such as, the chromatin remodeling gene ARID1A. Our aim was to determine the expression levels of four GC-related genes, ARID1A, CDH1, cMET and PIK3CA, and 14 target-related microRNAs (miRNAs). We compared mRNA and miRNA expression levels among 66 gastric tumor and normal adjacent mucosa samples using quantitative real-time reverse transcription PCR. Moreover, ARID1A, cMET and PIK3CA protein levels were assessed by immunohistochemistry (IHC). Finally, gene and miRNAs as…

Molecular profile in Paraguayan colorectal cancer patients, towards to a precision medicine strategy

[EN] Somatic mutation analysis and evaluation of microsatellite instability (MSI) have become mandatory for selecting personalized therapy strategies for advanced colorectal cancer and are not available as routine methods in Paraguay. The aims of this study were to analyze the molecular profile as well as the microsatellite status in a series of advanced colorectal patients from two public hospitals from Paraguay, to introduce these methodologies in the routine practice to guide the therapeutic decisions. Thirty-six patients diagnosed with advanced colorectal cancer from two referent public hospitals from Paraguay were recruited from May 2017 to February 2018. Sequenom Mass spectrometry, On…

Sex and MC1R variants in human pigmentation: Differences in tanning ability and sensitivity to sunlight between sexes

Sex-Specific Genetic Effects Associated with Pigmentation, Sensitivity to Sunlight, And Melanoma in a Population of Spanish Origin

Background Human pigmentation is a polygenic quantitative trait with high heritability. In addition to genetic factors, it has been shown that pigmentation can be modulated by oestrogens and androgens via up- or down-regulation of melanin synthesis. Our aim was to identify possible sex differences in pigmentation phenotype as well as in melanoma association in a melanoma case-control population of Spanish origin. Methods Five hundred and ninety-nine females (316 melanoma cases and 283 controls) and 458 males (234 melanoma cases and 224 controls) were analysed. We genotyped 363 polymorphisms (single nucleotide polymorphisms (SNPs)) from 65 pigmentation gene regions. Results When samples were…

Involvement of Different networks in mammary gland involution after the pregnancy/lactation cycle: Implications in breast cancer

Early pregnancy is associated with a reduction in a woman's lifetime risk for breast cancer. However, different studies have demonstrated an increase in breast cancer risk in the years immediately following pregnancy. Early and long-term risk is even higher if the mother age is above 35 years at the time of first parity. The proinflammatory microenvironment within the mammary gland after pregnancy renders an "ideal niche" for oncogenic events. Signaling pathways involved in programmed cell death and tissue remodeling during involution are also activated in breast cancer. Herein, the major signaling pathways involved in mammary gland involution, signal transducer and activator of transcripti…

Gene expression changes responsible for lapatinib acquired resistance in HER2 positive gastric cancer cell lines: a microarray analysis

First Nationwide Molecular Screening Program in Spain for Patients With Advanced Breast Cancer: Results From the AGATA SOLTI-1301 Study

Anàlisi de seqüències d'ADN; Subtipus PAM50; Genètica molecular Análisis de secuencias de ADN; Subtipo PAM50; Genética molecular DNA sequence analyses; PAM50 subtype; Molecular genetic Background: The SOLTI-1301 AGATA study aimed to assess the feasibility of a multi-institutional molecular screening program to better characterize the genomic landscape of advanced breast cancer (ABC) and to facilitate patient access to matched-targeted therapies in Spain. Methods: DNA sequencing of 74 cancer-related genes was performed using FFPE tumor samples in three different laboratories with three different gene panels. A multidisciplinary advisory board prospectively recommended potential targeted trea…

Epigenetic changes in localized gastric cancer: the role of RUNX3 in tumor progression and the immune microenvironment

// Marta Jessica Llorca-Cardenosa 1, * , Tania Fleitas 1, * , Maider Ibarrola-Villava 1 , Maria Pena-Chilet 1 , Cristina Mongort 2 , Carolina Martinez-Ciarpaglini 2 , Lara Navarro 2 , Valentina Gambardella 1 , Josefa Castillo 1 , Susana Rosello 1 , Samuel Navarro 2 , Gloria Ribas 1 , Andres Cervantes 1 1 Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain 2 Department of Pathology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain * These authors contributed equally to this work Correspondence to: Gloria Ribas, email: gribas@incliva.es Andres Cervantes, email: andres.cervantes@uv.es Keywords: RUNX3, ARID1A, gastric ca…