Continuous Risk Assessment of Late and Term Preeclampsia Throughout Pregnancy: A Retrospective Cohort Study.

: To evaluate the diagnostic accuracy of widely available biomarkers longitudinally measured throughout pregnancy to predict all and term (delivery at ≥37 weeks) preeclampsia (PE). : This is a longitudinal retrospective study performed at Hospital Universitario de Torrejón (Madrid, Spain) and Shterev Hospital (Sofia, Bulgaria) between August 2017 and December 2022. All pregnant women with singleton pregnancies and non-malformed live fetuses attending their routine ultrasound examination and first-trimester screening for preterm PE at 11 + 0 to 13 + 6 weeks' gestation at the participating centers were invited to participate in a larger study for the prediction of pregnancy complications.

Featuring BRCA1 and BRCA2 germline mutational landscape from Asturias (North Spain).

The singular BRCA1/2 mutational landscape of Asturias is updated 10 years after the first study. We analyzed BRCA1 and BRCA2 pathogenic variants in 1653 index cases. In total, 238 families were identified to carry a pathogenic variant, 163 families in BRCA1 and 75 families in BRCA2.

Analysis of extracellular matrix network dynamics in cancer using the MatriNet database.

The extracellular matrix (ECM) is a three-dimensional network of proteins of diverse nature, whose interactions are essential to provide tissues with the correct mechanical and biochemical cues they need for proper development and homeostasis. Changes in the quantity of extracellular matrix (ECM) components and their balance within the tumor microenvironment (TME) accompany and fuel all steps of tumor development, growth and metastasis, and a deeper and more systematic understanding of these processes is fundamental for the development of future therapeutic approaches. The wealth of "big data" from numerous sources has enabled gigantic steps forward in the comprehension of the oncogenic process, also impacting on our understanding of ECM changes in the TME.

PanCancer analysis of somatic mutations in repetitive regions reveals recurrent mutations in snRNA U2.

Current somatic mutation callers are biased against repetitive regions, preventing the identification of potential driver alterations in these loci. We developed a mutation caller for repetitive regions, and applied it to study repetitive non protein-coding genes in more than 2200 whole-genome cases. We identified a recurrent mutation at position c.

Circulating tumour DNA from the cerebrospinal fluid allows the characterisation and monitoring of medulloblastoma.

The molecular characterisation of medulloblastoma, the most common paediatric brain tumour, is crucial for the correct management and treatment of this heterogenous disease. However, insufficient tissue sample, the presence of tumour heterogeneity, or disseminated disease can challenge its diagnosis and monitoring. Here, we report that the cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) recapitulates the genomic alterations of the tumour and facilitates subgrouping and risk stratification, providing valuable information about diagnosis and prognosis.

Genomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes.

Mantle cell lymphoma (MCL) is a mature B-cell neoplasm initially driven by CCND1 rearrangement with 2 molecular subtypes, conventional MCL (cMCL) and leukemic non-nodal MCL (nnMCL), that differ in their clinicobiological behavior. To identify the genetic and epigenetic alterations determining this diversity, we used whole-genome (n = 61) and exome (n = 21) sequencing (74% cMCL, 26% nnMCL) combined with transcriptome and DNA methylation profiles in the context of 5 MCL reference epigenomes. We identified that open and active chromatin at the major translocation cluster locus might facilitate the t(11;14)(q13;32), which modifies the 3-dimensional structure of the involved regions.

Genomic and Epigenomic Alterations in Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia is a common disease in Western countries and has heterogeneous clinical behavior. The relevance of the genetic basis of the disease has come to the forefront recently, with genome-wide studies that have provided a comprehensive view of structural variants, somatic mutations, and different layers of epigenetic changes. The mutational landscape is characterized by relatively common copy number alterations, a few mutated genes occurring in 10-15% of cases, and a large number of genes mutated in a small number of cases.

Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.

In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas.

The U1 spliceosomal RNA is recurrently mutated in multiple cancers.

Cancers are caused by genomic alterations known as drivers. Hundreds of drivers in coding genes are known but, to date, only a handful of noncoding drivers have been discovered-despite intensive searching. Attention has recently shifted to the role of altered RNA splicing in cancer; driver mutations that lead to transcriptome-wide aberrant splicing have been identified in multiple types of cancer, although these mutations have only been found in protein-coding splicing factors such as splicing factor 3b subunit 1 (SF3B1).

Chromosome 12p Amplification in Triple-Negative/Mutated Breast Cancer Associates with Emergence of Docetaxel Resistance and Carboplatin Sensitivity.

Taxanes are the mainstay of treatment in triple-negative breast cancer (TNBC), with and acquired resistance limiting patient's survival. To investigate the genetic basis of docetaxel resistance in TNBC, exome sequencing was performed on matched TNBC patient-derived xenografts (PDX) sensitive to docetaxel and their counterparts that developed resistance upon continuous drug exposure. Most mutations, small insertions/deletions, and copy number alterations detected in the initial TNBC human metastatic samples were maintained after serial passages in mice and emergence of resistance.

Tumor xenograft modeling identifies an association between TCF4 loss and breast cancer chemoresistance.

Understanding the mechanisms of cancer therapeutic resistance is fundamental to improving cancer care. There is clear benefit from chemotherapy in different breast cancer settings; however, knowledge of the mutations and genes that mediate resistance is incomplete. In this study, by modeling chemoresistance in patient-derived xenografts (PDXs), we show that adaptation to therapy is genetically complex and identify that loss of transcription factor 4 (TCF4; also known as ITF2) is associated with this process.

Dissecting Degradomes: Analysis of Protease-Coding Genes.

Proteases constitute up to 3% of all protein-coding genes in a vertebrate genome and participate in numerous physiological and pathological processes. The characterization of the degradome of one organism, the set of all genes encoding proteolytic enzymes, and the comparison to the degradome of other species have proved useful to identify genetic differences that are helpful to elucidate the molecular basis of diverse biological processes, the different susceptibility to disease, and the evolution of the structure and function of proteases. Here we describe the main procedures involved in the characterization of the degradome of an organism for which its genome sequence is available.