A5025403673- Advanced Breast Cancer Therapies
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- BRCA gene mutations in cancer
- Lung Cancer Research Studies
- Prostate Cancer Treatment and Research
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- HER2/EGFR in Cancer Research
- PARP inhibition in cancer therapy
- Radiomics and Machine Learning in Medical Imaging
- RNA modifications and cancer
- Colorectal Cancer Treatments and Studies
- Helicobacter pylori-related gastroenterology studies
- Chronic Lymphocytic Leukemia Research
- Breast Cancer Treatment Studies
- Genomic variations and chromosomal abnormalities
- Advanced X-ray and CT Imaging
- Cancer Immunotherapy and Biomarkers
- Cancer-related molecular mechanisms research
- Neuroendocrine Tumor Research Advances
- Genomics and Rare Diseases
- Advanced Neuroimaging Techniques and Applications
- Ovarian cancer diagnosis and treatment
- Medical Imaging Techniques and Applications
University of Florence
2009-2025
Hospital of Prato
2017-2025
Azienda Usl Toscana Centro
2018-2024
Nuovo Ospedale di Prato
2019-2023
University of Trento
2016-2021
International Breast Cancer Study Group
2021
Weatherford College
2021
Dana-Farber Cancer Institute
2019
Brigham and Women's Hospital
2019
Harvard University
2019
Heterogeneity in the genomic landscape of metastatic prostate cancer has become apparent through several comprehensive profiling efforts, but little is known about impact this heterogeneity on clinical outcome. Here, we report and transcriptomic analysis 429 patients with castration-resistant (mCRPC) linked longitudinal outcomes, integrating findings from whole-exome, transcriptome, histologic analysis. For 128 treated a first-line next-generation androgen receptor signaling inhibitor (ARSI;...
Evading cancer drugs by identity fraud Prostate growth is fueled male hormones called androgens. Drugs targeting the androgen receptor (AR) are initially efficacious, but most tumors eventually become resistant (see Perspective Kelly and Balk). Mu et al. found that prostate cells escaped effects of deprivation therapy through a change in lineage identity. Functional loss tumor suppressors TP53 RB1 promoted shift from AR-dependent luminal epithelial to AR-independent basal-like cells. In...
Abstract A major hurdle in the study of rare tumors is a lack existing preclinical models. Neuroendocrine prostate cancer an uncommon and aggressive histologic variant that may arise de novo or as mechanism treatment resistance patients with pre-existing castration-resistant cancer. There are few available models to neuroendocrine Here, we report generation characterization tumor organoids derived from needle biopsies metastatic lesions four patients. We demonstrate genomic, transcriptomic,...
Abstract We developed a novel software tool, EXCAVATOR, for the detection of copy number variants (CNVs) from whole-exome sequencing data. EXCAVATOR combines three-step normalization procedure with heterogeneous hidden Markov model algorithm and calling method that classifies genomic regions into five states. validate on three datasets compare results other methods. These analyses show outperforms methods is therefore valuable tool investigation CNVs in largescale projects, as well clinical...
Loss of androgen receptor (AR) signaling dependence occurs in approximately 15%–20% advanced treatment-resistant prostate cancers, and this may manifest clinically as transformation from a adenocarcinoma histology to castration-resistant neuroendocrine cancer (CRPC-NE). The diagnosis CRPC-NE currently relies on metastatic tumor biopsy, which is invasive for patients sometimes challenging diagnose due morphologic heterogeneity. By studying whole-exome sequencing whole-genome bisulfite cell...
AURORA aims to study the processes of relapse in metastatic breast cancer (MBC) by performing multi-omics profiling on paired primary tumors and early-course metastases. Among 381 patients (primary tumor metastasis pairs: 252 targeted gene sequencing, 152 RNA 67 single nucleotide polymorphism arrays), we found a driver role for GATA1 MEN1 somatic mutations. Metastases were enriched ESR1, PTEN, CDH1, PIK3CA, RB1 mutations; MDM4 MYC amplifications; ARID1A deletions. An increase clonality was...
Abstract Motivation: The discovery of novel gene fusions can lead to a better comprehension cancer progression and development. emergence deep sequencing trancriptome, known as RNA-seq, has opened many opportunities for the identification this class genomic alterations, leading chimeric transcripts in melanomas, breast cancers lymphomas. Nowadays, few computational approaches have been developed detection transcripts. Although all these methods show good sensitivity, much work remains reduce...
Advanced prostate cancer initially responds to hormonal treatment, but ultimately becomes resistant and requires more potent therapies. One mechanism of resistance observed in around 10-20% these patients is lineage plasticity, which manifests a partial or complete small cell neuroendocrine (NEPC) phenotype. Here, we investigate the role mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex NEPC. Using large patient datasets, patient-derived organoids lines, identify mSWI/SNF subunits...
CDK4/6 inhibitors represent a new treatment standard for hormone receptor-positive (HR+), HER2-negative advanced breast cancer (BC) patients. Although efficacious, resistance to these agents is universal. Here, we profiled large panel of HR+ BC cell lines with conditioned the inhibitor palbociclib, and analyzed cycle-related markers by gene expression profiles (GEP) western blot (WB). GEP showed high molecular heterogeneity among models, E2F targets being significantly enriched both during...
Abstract Motivation: Runs of homozygosity (ROH) are sizable chromosomal stretches homozygous genotypes, ranging in length from tens kilobases to megabases. ROHs can be relevant for population and medical genetics, playing a role predisposition both rare common disorders. commonly detected by single nucleotide polymorphism (SNP) microarrays, but attempts have been made use whole-exome sequencing (WES) data. Currently available methods developed the analysis uniformly spaced SNP-array maps do...
The tumor suppressor protein retinoblastoma (RB) is mechanistically linked to suppression of transcription factor E2F1-mediated cell cycle regulation. For multiple types, loss RB function associated with poor clinical outcome. action abrogated either by direct depletion or through inactivation function; however, the basis for this selectivity unknown. Here, analysis samples and cell-free DNA from patients advanced prostate cancer showed that was preferred pathway disruption in human disease....
Tumor DNA circulates in the plasma of cancer patients admixed with from noncancerous cells. The genomic landscape has been characterized metastatic castration-resistant prostate (mCRPC) but methylome not extensively explored. Here, we performed next-generation sequencing (NGS) on and without bisulfite treatment mCRPC receiving either abiraterone or enzalutamide pre- post-chemotherapy setting. Principal component analysis indicated that main contributor to methylation variance (principal one,...
Abstract STUDY QUESTION What is the diagnostic potential of next generation sequencing (NGS) based on a ‘mouse azoospermia’ gene panel in human non-obstructive azoospermia (NOA)? SUMMARY ANSWER The performance genes associated with mouse was relatively successful idiopathic NOA patients and allowed discovery two novel involved due to meiotic arrest. WHAT IS KNOWN ALREADY largely heterogeneous clinical entity, which includes different histological pictures. In large proportion NOA, aetiology...
In the treatment of advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitors have shown remarkable results. However, not all patients with NSCLC respond to this drug or receive durable benefits. Thus, patient stratification and selection, as well identification predictive biomarkers, represent pivotal aspects address. framework, metabolomics can be used support discrimination between responders non-responders. Here, was analyze sera samples from 50 NSCL treated inhibitors....
Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) are highly effective against estrogen receptor-positive (ER+)/HER2- breast cancer; however, intrinsic acquired resistance is common. Elucidating the molecular features of sensitivity to CDK4/6i may lead identification predictive biomarkers novel therapeutic targets, paving way toward improving patient outcomes.Parental cancer cells their endocrine-resistant derivatives (EndoR) were used. Derivatives with palbociclib (PalboR)...
Castration-resistant prostate cancer (CRPC) is a heterogeneous disease associated with phenotypic subtypes that drive therapy response and outcome differences. Histologic transformation to castration-resistant neuroendocrine (CRPC-NE) distinct epigenetic alterations, including changes in DNA methylation. The current diagnosis of CRPC-NE challenging relies on metastatic biopsy. We developed targeted methylation assay detect using plasma cell-free (cfDNA). quantifies tumor content provides...
Targeting aromatase deprives ER + breast cancers of estrogens and is an effective therapeutic approach for these tumors. However, drug resistance unmet clinical need. Lipidomic analysis long-term estrogen-deprived (LTED) cancer cells, a model inhibitor resistance, revealed enhanced intracellular lipid storage. Functional metabolic showed that droplets together with peroxisomes, which we to be enriched active in the LTED controlled redox homeostasis conferred adaptability resistant This...
Next-generation sequencing might be particularly advantageous in genetically heterogeneous conditions, such as hypertrophic cardiomyopathy (HCM), which a considerable proportion of patients remain undiagnosed after Sanger. In this study, we present an Italian family with atypical HCM novel disease-causing variant α-actinin 2 (ACTN2) was identified by next-generation sequencing.A large spanning 4 generations examined, exhibiting autosomal dominant cardiomyopathic trait comprising variable...
Abstract Motivation: The advent of high-throughput sequencing technologies is revolutionizing our ability in discovering and genotyping DNA copy number variants (CNVs). Read count-based approaches are able to detect CNV regions with an unprecedented resolution. Although this computational strategy has been recently introduced literature, much work already done for the preparation, normalization analysis kind data. Results: Here we face many aspects that cover detection CNVs by using read...
Mutations in CCAAT/enhancer binding protein α (CEBPA) occur 5–10% of cases acute myeloid leukemia. CEBPA-double-mutated usually bear biallelic N- and C-terminal mutations are associated with a favorable clinical outcome. Identification CEBPA mutants is challenging because the variety mutations, intrinsic characteristics gene technical issues. Several screening methods (fragment-length analysis, expression array) have been proposed especially for large-scale use; although efficient, they...