A5072119941- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Gene expression and cancer classification
- Cancer Immunotherapy and Biomarkers
- Genetic factors in colorectal cancer
- RNA and protein synthesis mechanisms
- Bioinformatics and Genomic Networks
- Cancer-related molecular mechanisms research
- Lung Cancer Research Studies
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- HER2/EGFR in Cancer Research
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Sarcoma Diagnosis and Treatment
- Genomics and Phylogenetic Studies
- Cardiac tumors and thrombi
- Colorectal Cancer Treatments and Studies
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Rare Diseases
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Molecular Biology Techniques and Applications
- Cancer Mechanisms and Therapy
Italian institute for Genomic Medicine
2018-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2019-2024
University of Milan
2022-2024
Candiolo Cancer Institute
2019-2022
King's College London
2016-2017
The Francis Crick Institute
2017
European Institute of Oncology
2013-2014
MRC Laboratory of Molecular Biology
2008-2014
IRCCS Eugenio Medea
2006-2011
Medical Research Council
2011
Ubiquitination is one of the main post-translational modification proteins. It plays key roles in a broad range cellular functions, including protein degradation, interactions, and subcellular location. In ubiquitination system, different proteins are involved their dysregulation can lead to various human diseases, cancers. By using data available from Cancer Genome Atlas (TCGA) Genotype-Tissue Expression (GTEx) databases, we here show that ubiquitin conjugating enzyme, E2C (UBE2C),...
Selective KRAS
// Lorena Benedetti 1, 2 , Matteo Cereda LeeAnn Monteverde Nikita Desai and Francesca D. Ciccarelli 1 Division of Cancer Studies, King’s College London, London SE1 1UL, UK Systems Biology Laboratory, The Francis Crick Institute, NW1 1AT, Correspondence to: Ciccarelli, email: francesca.ciccarelli@kcl.ac.uk Keywords: synthetic lethality, cohesin complex, paralog dependency, cancer vulnerability, precision medicine Received: September 20, 2016 Accepted: March...
Abstract Background The “HER2-low” nomenclature identifies breast carcinomas (BCs) displaying a HER2 score of 1+/2+ in immunohistochemistry and lacking ERBB2 amplification. Whether HER2-low BCs (HLBCs) constitute distinct entity is debated. Methods We performed DNA RNA high-throughput analysis on 99 HLBC samples ( n = 34 cases with 1+/HLBC-1, 15 2+ not amplified/HLBC-2N, 50 copy number the equivocal range/HLBC-2E). compared mutation rates data from 1317 Memorial Sloan-Kettering Cancer Center...
In vivo apoptosis of human mesenchymal stromal cells (MSCs) plays a critical role in delivering immunomodulation. Yet, caspase activity not only mediates the dying process but also death-independent functions that may shape immunogenicity apoptotic cells. Therefore, better characterization immunological profile MSCs (ApoMSCs) could shed light on their mechanistic action and therapeutic applications. We analyzed transcriptomes undergoing identified several immunomodulatory factors chemokines...
Abstract RNA-binding proteins (RBPs) regulate splicing according to position-dependent principles, which can be exploited for analysis of regulatory motifs. Here we present RNAmotifs, a method that evaluates the sequence around differentially regulated alternative exons identify clusters short and degenerate sequences, referred as multivalent RNA We show diverse RBPs share basic positional but differ in their propensity enhance or repress exon inclusion. assess spliced between brain heart,...
Abstract Synchronous colorectal cancers (syCRCs) are physically separated tumours that develop simultaneously. To understand how the genetic and environmental background influences development of multiple tumours, here we conduct a comparative analysis 20 syCRCs from 10 patients. We show have independent origins, acquire dissimilar somatic alterations, different clone composition. This inter- intratumour heterogeneity must be considered in selection therapy monitoring resistance. SyCRC...
Dysregulation of alternative splicing in prostate cancer is linked to transcriptional programs activated by AR, ERG, FOXA1, and MYC. Here, we show that FOXA1 functions as the primary orchestrator dysregulation across 500 metastatic transcriptomes. We demonstrate binds regulatory regions splicing-related genes, including HNRNPK SRSF1. By controlling trans-acting factor expression, exploits an "exon definition" mechanism calibrating toward dominant isoform production. This regulation...
Mammalian genomes consist of regions differing in GC content, referred to as isochores or GC-content domains. The scientific debate is still open whether such compositional heterogeneity a selected neutral trait.Here we analyze SNP allele frequencies, retrotransposon insertion polymorphisms (RIPs), well fixed substitutions accumulated the human lineage since its divergence from chimpanzee indicate that biased gene conversion (BGC) has been playing role within-genome content variation. Yet,...
The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes individual patients considering all types damaging simultaneously. Analysing 261 EACs from the OCCAMS Consortium, discover helper that, alongside well-known drivers, promote cancer. We confirm robustness our approach 107 additional EACs. Unlike...
Abstract Background Duchenne and Becker Muscular dystrophies (DMD/BMD) are allelic disorders caused by mutations in the dystrophin gene, which encodes a sarcolemmal protein responsible for muscle integrity. Deletions duplications account approximately 75% of DMD 85% BMD. The implementation techniques allowing complete gene sequencing has focused attention on small point other mechanisms underlying complex rearrangements. Methods We selected 47 patients (41 families; 35 DMD, 6 BMD) without...
Abstract The onset of multiple and metachronous tumors in young patients induces to suspect the presence genetic variants genes associated with tumorigenesis. We describe here unusual case a 16-year-old patient who developed synchronous bifocal colorectal adenocarcinoma distant metastases. provide high throughput molecular characterization whole-exome sequencing (WES) DNA targeted different tumoral lesions normal tissue samples that led unveil germline POLE mutation (p.Ser297Cys) coexisting...
We propose a C++ class library developed to the purpose of making implementation sequence analysis algorithms easier and faster when genomic annotations variations need be considered. The provides hierarchy seamlessly bind together elements sequences algorithm results; it allows evaluate effect mutations/variations in terms both element position shifts results, limiting recalculation minimum. Particular care has been posed keep memory time overhead into acceptable limits.A complete tutorial...
Abstract Background Transposable elements (TEs) represent more than 45% of the human and mouse genomes. Both parasitic mutualistic features have been shown to apply host-TE relationship but a comprehensive scenario forces driving TE fixation within mammalian genes is still missing. Results We show that intronic multispecies conserved sequences (MCSs) affecting integration frequency over time. verify selective economizing pressure has acting on TEs decrease their in highly expressed genes....
Cancer genetic heterogeneity offers a wide repertoire of molecular determinants to be screened as therapeutic targets. Here, we identify potential anticancer targets by exploiting negative interactions between genes with driver loss-of-function mutations (recessive cancer genes) and their functionally redundant paralogs. We recessive additional copies experimentally test our predictions on three paralogous pairs. confirm digenic two (SMARCA4 CDH1) corresponding paralogs (SMARCA2 CDH3)....
The vasopressin receptor type 1b (AVPR1B) is mainly expressed by pituitary corticotropes and it mediates the stimulatory effects of AVP on ACTH release; common AVPR1B haplotypes have been involved in mood anxiety disorders humans, while rodents lacking a functional gene display behavioral defects altered stress responses.
Formalin-fixed paraffin-embedded (FFPE) samples represent the cornerstone of tissue-based analysis in precision medicine. Targeted next-generation sequencing panels are routinely used to analyze a limited number genes guide treatment decision-making for advanced-stage patients. The and complexity genetic alterations be investigated rapidly growing; several instances, comprehensive genomic profiling is needed. poor quality material extracted from FFPE may impact feasibility/reliability data....