Clinicopathological Profiles Associated with Discordant Mutational Status between Liquid and Tissue Biopsies in a Real-World Cohort of Metastatic Colorectal Cancer.

We aimed to identify common mCRC profiles associated with a discordant mutational status of between the standard of care (SoC) tumour tissue tests and ctDNA tests to understand ctDNA detection and improve treatment responses. This was a multicentre, retrospective and prospective study. A total of 366 Spanish mCRC patients were independently recruited.

Evaluation of a Targeted Next-Generation Sequencing Panel for the Non-Invasive Detection of Variants in Circulating DNA of Colorectal Cancer.

Molecular profiling of circulating cell-free DNA (cfDNA) has shown utility for the management of colorectal cancer (CRC). TruSight Tumor 170 (TST170) is a next-generation sequencing (NGS) panel that covers 170 cancer-related genes, including , which is a key driver gene in CRC. We evaluated the capacity of TST170 to detect gene variants in cfDNA from a retrospective cohort of 20 metastatic CRC patients with known variants in tumor tissue and in cfDNA previously analyzed by pyrosequencing and BEAMing, respectively.

STATegra, a comprehensive multi-omics dataset of B-cell differentiation in mouse.

Multi-omics approaches use a diversity of high-throughput technologies to profile the different molecular layers of living cells. Ideally, the integration of this information should result in comprehensive systems models of cellular physiology and regulation. However, most multi-omics projects still include a limited number of molecular assays and there have been very few multi-omic studies that evaluate dynamic processes such as cellular growth, development and adaptation.

Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation.

The differentiation of self-renewing progenitor cells requires not only the regulation of lineage- and developmental stage-specific genes but also the coordinated adaptation of housekeeping functions from a metabolically active, proliferative state toward quiescence. How metabolic and cell-cycle states are coordinated with the regulation of cell type-specific genes is an important question, because dissociation between differentiation, cell cycle, and metabolic states is a hallmark of cancer. Here, we use a model system to systematically identify key transcriptional regulators of Ikaros-dependent B cell-progenitor differentiation.

Direct interaction of Ikaros and Foxp1 modulates expression of the G protein-coupled receptor G2A in B-lymphocytes and acute lymphoblastic leukemia.

Ikaros and Foxp1 are transcription factors that play key roles in normal lymphopoiesis and lymphoid malignancies. We describe a novel physical and functional interaction between the proteins, which requires the central zinc finger domain of Ikaros. The Ikaros-Foxp1 interaction is abolished by deletion of this region, which corresponds to the IK6 isoform that is commonly associated with high-risk acute lymphoblastic leukemia (ALL).

Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation.

Ikaros family DNA-binding proteins are critical regulators of B-cell development. Because the current knowledge of Ikaros targets in B-cell progenitors is limited, we have identified genes that are bound and regulated by Ikaros in pre-B cells. To elucidate the role of Ikaros in B-cell lineage specification and differentiation, we analyzed the differential expression of Ikaros targets during the progression of multipotent to lymphoid-restricted progenitors, B- and T-cell lineage specification, and progression along the B-cell lineage.

Analysis of the functional relevance of a putative regulatory SNP of PDCD1, PD1.3, associated with systemic lupus erythematosus.

This study aimed to test the functional effects of the PD1.3 single nucleotide polymorphism (SNP) (rs11568821), which were proposed based on its association to systemic lupus erythematosus (SLE) susceptibility and in electrophoretic mobility shift assays (EMSA) results. We analysed transcriptional effects of the PD1.

Bias in association studies of systemic lupus erythematosus susceptibility due to geographical variation in the frequency of a programmed cell death 1 polymorphism across Europe.

We obtained eight collections of DNA samples from ethnically matched systemic lupus erythematosus (SLE) patients and controls from five European countries totaling 783 patients and 1210 controls. A highly significant cline in the frequency of the PD1.3 A allele was found among controls but not among SLE patients.

SUMO4 and MAP3K7IP2 single nucleotide polymorphisms and susceptibility to rheumatoid arthritis.

Objective: To explore the role of single nuclear polymorphisms (SNP) in 2 candidate genes, SUMO4 and MAP3K7IP2, in susceptibility to rheumatoid arthritis (RA).

Methods: Two cohorts from different Spanish towns totalling 635 patients with RA and 826 controls were studied. Six SNP were genotyped by matrix assisted laser desorption-ionization time-of-flight (MALDI-TOF) with the MassARRAY SNP genotyping system.

Association of a non-synonymous single-nucleotide polymorphism of DNASEI with SLE susceptibility.

Objectives: To investigate the association of a non-synonymous single-nucleotide polymorphism (SNP) in DNASEI with susceptibility to systemic lupus erythematosus (SLE) and the production of autoantibodies to nuclear antigens.

Methods: The Gln244Arg (rs1053874) SNP was studied in 276 SLE patients and in 368 healthy controls of Spanish ancestry. Its relationship with SLE susceptibility, serum DNase I activity, anti-ribonucleoprotein (RNP), anti-double-stranded DNA (dsDNA), anti-nucleosome and anti-single-stranded DNA (ssDNA) antibodies was determined.

Association of PDCD1 with susceptibility to systemic lupus erythematosus: evidence of population-specific effects.

Objective: The A allele of the PD1.3 single-nucleotide polymorphism (SNP) on the programmed cell death gene PDCD1 was markedly more frequent in patients with systemic lupus erythematosus (SLE) than in unaffected controls in a recent study involving large sets of Swedish, European American, and Mexican families. This study sought to determine the role of PDCD1 in susceptibility to SLE in the Spanish population.

CARD15/NOD2 analysis in rheumatoid arthritis susceptibility.

Objective: To determine if the mutations in the CARD15/NOD2 gene predisposing to Crohn's disease (CD) contribute also to the genetic susceptibility to rheumatoid arthritis (RA).

Methods: The frequencies of the three commonest mutations of CARD15/NOD2 predisposing to CD (2104C > T, 2722G>C and 3020insC) were determined in 210 RA patients and 227 controls.

Results: Allelic frequencies of the CARD15/NOD2 mutations in RA patients (2104C>T, 2.

The three most common CARD15 mutations associated with Crohn's disease and the chromosome 16 susceptibility locus for systemic lupus erythematosus.

Objective: To test if the three most common mutations contributing to Crohn's disease on the CARD15/NOD2 gene could contribute also to genetic susceptibility to systemic lupus erythematosus (SLE), which has been found to be linked to the region of chromosome 16q13 where the CARD15 gene is located.

Methods: We obtained DNA samples from the blood of 189 SLE patients (according to the American College of Rheumatology classification criteria) and 194 controls of Spanish ancestry. Genotypes for the three CARD15 mutations (3020insC, 2722G>C and 2104C>T) were determined by hybridization with fluorescence resonance energy transfer probes on a LightCycler real-time polymerase chain reaction system.

Lack of association of ankylosing spondylitis with the most common NOD2 susceptibility alleles to Crohn's disease.

Objective: To investigate whether the 3 most common mutations in the NOD2 gene that confer susceptibility to Crohn's disease (CD) are also associated with ankylosing spondylitis (AS).

Methods: DNA from 112 patients with AS and 168 controls of homogenous Spanish ancestry were studied. The frequencies of the pathogenic alleles of NOD2 (3020insC, 2722G>C, and 2104C>T) were determined by analysis of the melting curves after hybridization with FRET probes on a Light Cycler real-time polymerase chain reaction (PCR) system.