Alejandro Moles‐Fernández
A5059691470- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Radiomics and Machine Learning in Medical Imaging
- Genomics and Rare Diseases
- BRCA gene mutations in cancer
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Genomic variations and chromosomal abnormalities
- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Nutrition, Genetics, and Disease
- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- Genetics, Bioinformatics, and Biomedical Research
- Genetics and Neurodevelopmental Disorders
- Cancer-related Molecular Pathways
- Cervical Cancer and HPV Research
Vall d'Hebron Hospital Universitari
2021-2025
Vall d'Hebron Institut de Recerca
2019-2024
Vall d'Hebron Institute of Oncology
2018-2023
Cancer Genetics (United States)
2021
Universitat Autònoma de Barcelona
2019
CIBBIM-Nanomedicine
2018
Research Article30 October 2018Open Access Source DataTransparent process A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation Marta Castroviejo-Bermejo Experimental Therapeutics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain Search for more papers by this author Cristina Cruz High Risk and Familial Cancer Department Medical Hospital d'Hebron, Universitat Autònoma de Alba Llop-Guevara Sara Gutiérrez-Enríquez Oncogenetics Mandy Ducy...
Poly (ADP-ribose) polymerase 1 and 2 (PARP1/2) inhibitors (PARPi) are targeted therapies approved for homologous recombination repair (HRR)-deficient breast, ovarian, pancreatic, prostate cancers. Since inhibition of PARP1 is sufficient to cause synthetic lethality in tumors with deficiency (HRD), selective such as saruparib (AZD5305) being developed. It expected that leads a safer profile facilitates its combination other DNA damage inhibitors. Here, we aimed characterize the antitumor...
Abstract PARP inhibitors (PARPi) are approved drugs for platinum-sensitive, high-grade serous ovarian cancer (HGSOC) and breast, prostate, pancreatic cancers (PaC) harboring genetic alterations impairing homologous recombination repair (HRR). Detection of nuclear RAD51 foci in tumor cells is a marker HRR functionality, we previously established test to detect foci. Here, aimed validate the score cut off compare performance this other deficiency (HRD) detection methods. Laboratory models from...
In silico tools for splicing defect prediction have a key role to assess the impact of variants uncertain significance. Our aim was evaluate performance set commonly used in comparing predictions against RNA vitro results. This done natural splice sites clinically relevant genes hereditary breast/ovarian cancer (HBOC) and Lynch syndrome. A study divided into two stages SSF-like, MaxEntScan, NNSplice, HSF, SPANR dbscSNV tools. discovery dataset 99 with unequivocal results studies, located 10...
Background Genetic analysis of BRCA1 and BRCA2 for the diagnosis hereditary breast ovarian cancer (HBOC) is commonly restricted to coding regions exon-intron boundaries. Although germline pathogenic variants in these explain about ~20% HBOC cases, there still an important fraction that remains undiagnosed. We have screened BRCA1/2 deep intronic identify potential spliceogenic could part missing susceptibility. Methods analysed by targeted gene sequencing 192 high-risk families testing...
The contribution of deep intronic splice-altering variants to hereditary breast and ovarian cancer (HBOC) is unknown. Current computational in silico tools predict spliceogenic leading pseudoexons have limited efficiency. We assessed the performance SpliceAI tool combined with ESRseq scores identify by affecting cryptic sites or splicing regulatory elements (SREs) using literature experimental datasets. Our results 233 published showed that SpliceAI, a 0.05 threshold, predicts splice sites,...
To investigate the performance of an in-house tumor sequencing panel to identify patients with breast cancer and a germline pathogenic variant (gPV). Retrospective blinded analysis in 90 prior genetic testing (45 non-carriers 45 carriers gPV) using (VHIO-300). Sensitivity (S), specificity (Sp), positive predictive value (PPV), negative (NPV) were calculated. A Cohen's kappa coefficient ≥0.80 was predefined as minimum be reliably acceptable for clinical implementation. The cohort included 84...
Abstract Background Gene panel testing by massive parallel sequencing has increased the diagnostic yield but also number of variants uncertain significance. Clinical interpretation genomic data requires expertise for each gene and disease. Heterozygous ATM pathogenic increase risk cancer, particularly breast cancer. For this reason, is included in most hereditary cancer panels. It a large gene, showing high variants, them Hence, we initiated collaborative effort to improve standardize...
Testing for variation in BRCA1 and BRCA2 (commonly referred to as BRCA1/2), has emerged a standard clinical practice is helping countless women better understand manage their heritable risk of breast ovarian cancer. Yet the increased rate BRCA1/2 testing led an increasing number Variants Uncertain Significance (VUS), VUS discovery currently outpaces variant interpretation. Computational prediction key component interpretation pipeline. In CAGI5 ENIGMA Challenge, six teams submitted...
The widespread use of next generation sequencing for clinical testing is detecting an escalating number variants in noncoding regions the genome. significance majority these currently unknown, which presents a significant challenge. We have screened over 6,000 early-onset and/or familial breast cancer (BC) cases collected by ENIGMA consortium sequence 5′ BC susceptibility genes BRCA1 and BRCA2, identified 141 rare with global minor allele frequency < 0.01, 76 not been reported previously....
Abstract Bi-allelic loss-of-function (LoF) variants in the base excision repair (BER) gene NTHL1 cause a high-risk hereditary multi-tumor syndrome that includes breast cancer, but contribution of heterozygous to cancer is unknown. An analysis 4985 women with enriched for familial features, and 4786 cancer-free revealed significant enrichment LoF variants. Immunohistochemistry confirmed reduced expression tumors from carriers bi-allelic loss characteristic mutational signature (SBS 30) was...
BRCA1 and BRCA2 (BRCA1/2) germline variants disrupting the DNA protective role of these genes increase risk hereditary breast ovarian cancers. Correct identification then becomes clinically relevant, because it may survival rates carriers. Unfortunately, we are still unable to systematically predict impact BRCA1/2 variants. In this article, present a family in silico predictors that address problem, using gene-specific approach. For each protein, have developed two tools, aimed at predicting...
Establishing the pathogenic nature of variants in ATM, a gene associated with breast cancer and other hereditary cancers, is crucial for providing patients adequate care. Unfortunately, achieving good variant classification still difficult. To address this challenge, we extended range silico tools series graphical devised analysis computational evidence by health care professionals. We propose family fast easy-to-use representations which impact considered relative to benign variants....
BRCA1 and BRCA2 (BRCA1/2) genetic variants that disrupt messenger RNA splicing are commonly associated with increased risks of developing breast/ovarian cancer. The majority studies published to date rely on qualitative methodologies (i.e., Sanger sequencing), but it is necessary incorporate semi-quantitative or quantitative approaches accurately interpret the clinical significance spliceogenic variants. Here, we characterize impact 31 BRCA1/2 using capillary electrophoresis fluorescent...
Accurate classification of genetic variants is crucial for clinical decision-making in hereditary cancer. In Spain, diagnostic laboratories have traditionally approached this task independently due to the lack a dedicated resource. Here we present SpadaHC, web-based database sharing cancer genes Spanish population. SpadaHC implemented using three-tier architecture consisting relational database, web tool and bioinformatics pipeline. Contributing can share variant classifications from...
Women with MPPV in BC genes have broad risk estimates. Follow-up and prevention guidelines often employ a one-size-fits-all approach. However, the PRS may help stratify risk. We aimed to evaluate change stratification when adding classical factors healthy women harboring MPPV. Multicentric study of aged 30-70 germline pathogenic variant PALB2, CHEK2, ATM, BARD1, or RAD51C/D available breast density (BD). Genotyping employed PRiSma-268 array. Cumulative 10-year was calculated using BOADICEA...
<div>Abstract<p>PARP inhibitors (PARPi) are approved drugs for platinum-sensitive, high-grade serous ovarian cancer (HGSOC) and breast, prostate, pancreatic cancers (PaC) harboring genetic alterations impairing homologous recombination repair (HRR). Detection of nuclear RAD51 foci in tumor cells is a marker HRR functionality, we previously established test to detect foci. Here, aimed validate the score cut off compare performance this other deficiency (HRD) detection methods....
Supplementary Data from Preclinical <i>In Vivo</i> Validation of the RAD51 Test for Identification Homologous Recombination-Deficient Tumors and Patient Stratification