Project description:Anal squamous cell carcinoma (ASCC) is an infrequent tumor. Since 70s, treatment of stages II-III consists on a combination of 5-fluorouracil (5FU), mitomycin C (MMC), and radiotherapy. The aim of this study is the identification of biomarkers that allow personalized treatment and improvement of therapeutic outcomes. Forty-six tumor paraffin samples from ASCC patients were analyzed by whole-exome sequencing. Single nucleotide polymorphisms and copy number variants (CNVs) were identified and their relation to disease-free survival (DFS) was studied using BRB Array Tool and Kaplan-Meier analyses. Obtained findings were validated in an independent retrospective cohort of 101 ASCC patients with stages I-III from eleven hospitals within the Multidisciplinary Spanish Digestive Cancer Group (GEMCAD) using qPCR Copy Number Assays. GEMCAD validation cohort was also analyzed using mass spectrometry proteomics to assess the biological features of these tumors.
Project description:SPO11-promoted DNA double-strand breaks (DSBs) formation is a crucial step for meiotic recombination, and it is indispensable to detect the broken DNA ends accurately for dissecting the molecular mechanisms behind. Here, we report a novel technique, named DEtail-seq (DNA End tailing followed by sequencing), that can directly and quantitatively capture the meiotic DSB 3’ overhang hotspots at single-nucleotide resolution.
Project description:Effective molecular diagnosis of congenital diseases hinges on comprehensive genomic analysis, traditionally reliant on various methodologies specific to each variant type — whole exome or genome sequencing for single nucleotide variants (SNVs), array CGH for copy-number variants (CNVs), and microscopy for structural variants (SVs). We introduce a novel, integrative approach combining exome sequencing with chromosome conformation capture, termed Exo-C. This method enables the concurrent identification of SNVs in clinically relevant genes and SVs across the genome and allows analysis of heterozygous and mosaic carriers. Enhanced with targeted long-read sequencing, Exo-C evolves into a cost-efficient solution capable of resolving complex SVs at base-pair accuracy. Through several case studies, we demonstrate how Exo-C's multifaceted application can effectively uncover diverse causative variants and elucidate disease mechanisms in patients with rare disorders.
