Descubrimiento de nuevas dianas terapéuticas en cáncer de mama basado en el análisis de metilación del ARNm.

148 p.N6-metiladenosina (m6A) es una de las modificaciones más abundante del ARNm presente en los organismos eucariotas. Distintos estudios han revelado que la modificación m6A está involucrada en la regulación de la mayoría de los procesos del metabolismo del ARNm. Sin embargo, aún no existe mucho conocimiento acerca del impacto que esta modificación tiene sobre la regulación de la expresión génica, su función en los procesos celulares y el efecto que puede ejercer en el desarrollo y progresión de ciertas enfermedades, como, por ejemplo, el cáncer de mama. Por tal motivo, en este estudio, exploramos la presencia de la modificación m6A en el cáncer de mama, específicamente en los subtipos moleculares luminal A, luminal B HER2-, luminal B HER2+, HER2+ y triple negativo, con el fin de determinar el estado de la metilación del ARN y de su posible relación con futuras dianas terapéuticas. Para ello, se ha evaluado el estado de la metilación m6A y de la expresión de las principales metiltransferasas y desmetilasas en muestras provenientes de los mencionados subtipos moleculares de cáncer de mama. También, se han identificado m6A-SNPs relacionados con esta enfermedad y se ha determinado el perfil de metilación m6A presente en todo el transcriptoma de los distintos subtipos moleculares mediante el uso de la técnica MeRIP-seq. Los resultados obtenidos muestran la presencia de metilación m6A en numerosos ARNms de genes altamente relacionados con el inicio y desarrollo tumorales lo que genera nuevas vías de estudio en esta enfermedad

Association of LCT -13910C>T polymorphism and hip fracture in a cohort of older adult population from Northern Spain

This work was supported by the Basque Government (IT-833-13, IT-1271-19, and predoctoral fellowship PRE_2019_2_0005 to TK) and the Carlos III Health Institute (PI06-0034)

In silico identification and in vitro expression analysis of breast cancer-related m6A-SNPs

Research on m6A-associated SNPs (m6A-SNPs) has emerged recently due to their possible critical roles in many key biological processes. In this sense, several investigations have identified m6A-SNPs in different diseases. In order to gain a more complete understanding of the role that m6A-SNPs can play in breast cancer, we performed an in silico analysis to identify the m6A-SNPs associated with breast cancer and to evaluate their possible effects. For this purpose, we downloaded SNPs related to breast cancer and a list of m6A-SNPs from public databases in order to identify which ones appear in both. Subsequently, we assessed the identified m6A-SNPs in silico by expression quantitative trait loci (eQTL) analysis and differential gene expression analysis. We genotyped the m6A-SNPs found in the in silico analysis in 35 patients with breast cancer, and we carried out a gene expression analysis experimentally on those that showed differences. Our results identified 981 m6A-SNPs related to breast cancer. Four m6A-SNPs showed an eQTL effect and only three were in genes that presented an altered gene expression. When the three m6A-SNPs were evaluated in the tissue sample of our breast cancer patients, only the m6A-SNP rs76563149 located in ZNF354A gene presented differences in allele frequencies and a low gene expression in breast cancer tissues, especially in luminal B HER2+ subtype. Future investigations of these m6A-SNPs should expand the study in different ethnic groups and increase the sample sizes to test their association with breast cancer and elucidate their molecular function

Development and validation of a new multiplex for upgrading Y-STRs population databases from 12 to 23 markers and its forensic casework application.

Y chromosomal short tandem repeats (Y-STRs) are used in forensic investigations as a useful complementary tool to autosomal markers. The ongoing development of new kits with an increasing number of markers makes it necessary to update populations typed in the Y-STR Haplotype Reference Database to reach at least 23 Y-STRs. A novel Y-STR multiplex panel was developed to offer a cost-efficient alternative to update Y-STR haplotypes from 12 to 23 loci. This panel includes the eleven markers, DYS448, DYS456, DYS458, DYS635, Y-GATA H4, DYS576, DYS481, DYS549, DYS533, DYS570 and DYS643, as well as DYS385a/b for traceability purpose. Developmental validation of this panel was conducted following the recommendations of the Scientific Working Group on DNA Analysis Methods (SWGDAM), showing high sensitivity, tolerance to common inhibitors as well as high species specificity. It was efficient for degraded DNA samples and for detection of male mixtures. When applying it for extending the current data of the Ibiza population, both the discrimination capacity and the haplotype diversity increased from 0.5952 to 0.9048 and from 0.9808 to 0.9977, respectively. Together, the study demonstrates the suitability of this panel in forensic casework.Authors acknowledge funding support from Basque Government under predoctoral fellowship PRE_2021_2_0157 to BNL, PRE_2021_2_0252 to EGR and PRE_2019_2_0005 to TK. Funds were provided by the Basque Government (Grupo Consolidado IT-1271-19)