Jacopo Azzollini
A5031671598- BRCA gene mutations in cancer
- Genetic Associations and Epidemiology
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Genomic variations and chromosomal abnormalities
- Cancer Genomics and Diagnostics
- Nutrition, Genetics, and Disease
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Genetic factors in colorectal cancer
- Male Breast Health Studies
- Ovarian cancer diagnosis and treatment
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- PARP inhibition in cancer therapy
- Bioinformatics and Genomic Networks
- Breast Lesions and Carcinomas
- Gene expression and cancer classification
- Genomics and Rare Diseases
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Genetic Syndromes and Imprinting
- RNA regulation and disease
- Hereditary Neurological Disorders
- Neurological diseases and metabolism
Fondazione IRCCS Istituto Nazionale dei Tumori
2015-2024
Wellcome Sanger Institute
2017
National Research Council
2016
University of Milan
2010-2015
Medical Genetics Center
2014
Department of Medical Sciences
2014
Fondazione IRCCS Istituto Neurologico Carlo Besta
2012
Ospedale San Paolo
2010
The prevalence and spectrum of germline mutations in BRCA1 BRCA2 have been reported single populations, with the majority reports focused on White Europe North America. Consortium Investigators Modifiers BRCA1/2 (CIMBA) has assembled data 18,435 families 11,351 ascertained from 69 centers 49 countries six continents. This study comprehensively describes characteristics 1,650 unique 1,731 deleterious (disease-associated) identified CIMBA database. We observed substantial variation mutation...
Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify risks for female carriers mutations. We investigated—for first time to our knowledge—associations common with male BRCA1/ 2 implications prediction. Materials Methods genotyped 1,802 from Consortium Investigators Modifiers by using custom Illumina OncoArray. investigated combined effects established susceptibility on constructing weighted polygenic scores (PRSs) published effect...
Abstract Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood spleen. Using expression quantitative trait loci (eQTL) reported these identify 26 previously unreported, likely target genes of overall risk variants, 17 for estrogen receptor (ER)-negative cancer, several with a known function. We...
We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with risks BRCA1 and BRCA2 pathogenic variant carriers. Retrospective cohort data on 18,935 12,339 female carriers of European ancestry were available. Three versions a 313 single-nucleotide polymorphism (SNP) BC PRS evaluated based whether they predict overall, estrogen receptor (ER)-negative, ER-positive BC, two overall high-grade serous EOC. Associations...
PurposeMonoallelic germ-line mutations in the BRCA1/FANCS, BRCA2/FANCD1 and PALB2/FANCN genes confer high risk of breast cancer. Biallelic these cause Fanconi anemia (FA), characterized by malformations, bone marrow failure, chromosome fragility, cancer predisposition (BRCA2/FANCD1 PALB2/FANCN), or an FA-like disease presenting a phenotype similar to FA but without failure (BRCA1/FANCS). FANCM monoallelic have been reported as moderate factors for cancer, there are no reports any clinical...
Cornelia de Lange syndrome (CdLS) and KBG are two distinct developmental pathologies sharing common features such as intellectual disability, psychomotor delay, some craniofacial limb abnormalities. Mutations in one of the five genes NIPBL, SMC1A, SMC3, HDAC8 or RAD21, were identified at least 70% patients with CdLS. Consequently, additional causative genes, either unknown responsible partially merging entities, possibly account for remaining 30% patients. In contrast, has only been...
Breast cancer (BC) in men is rare and genetic predisposition likely to play a relevant role its etiology. Inherited mutations BRCA1/2 account for about 13% of all cases additional genes that may contribute the missing heritability need be investigated. In our study, well‐characterized series 523 male BC (MBC) patients from Italian multicenter study on MBC, enriched non‐ MBC cases, was screened by multigene custom panel 50 cancer‐associated genes. The main clinical‐pathologic characteristics...
Abstract Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs BRCA1/2 were overall cancer high grade (Gleason 8+) using an international sample 65 171 male PSV carriers cancer, 3,388 2,880 without the 3′ region (c.7914+) significantly elevated compared reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25–2.52; P 0.001], as well Gleason 8+ (HR 3.11; CI, 1.63–5.95;...
Abstract Previous transcriptome‐wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome‐wide (GWAS), but analyses of subtype‐specific associations been limited. In this study, we conducted a TWAS using gene GTEx summary statistics the hitherto largest GWAS meta‐analysis for overall, estrogen receptor subtypes (ER+ ER−). We further compared with ER+ ER− subtypes, case‐only approach. also multigene conditional in...
Cornelia de Lange syndrome (CdLS) is a clinically heterogeneous disorder characterized by typical facial dysmorphism, cognitive impairment and multiple congenital anomalies. Approximately 75% of patients carry variant in one the five cohesin-related genes NIPBL, SMC1A, SMC3, RAD21 HDAC8. Herein we report on clinical molecular characterization 11 carrying 10 distinct variants Given high number identified so far, advise sequencing HDAC8 as an indispensable part routine diagnostic for with CdLS...
Recent population-based female breast cancer and prostate polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with risks for male BRCA1 BRCA2 pathogenic variant carriers.
The investigation of multiple molecular targets with next-generation sequencing (NGS) has entered clinical practice in oncology, yielding to a paradigm shift from the histology-centric approach mutational model for personalized treatment. Accordingly, most drugs recently approved oncology are coupled specific biomarkers. One potential tool implementing precision daily is represented by Molecular Tumor Board (MTB), multidisciplinary team whereby pathologists, biologists, bioinformaticians,...
BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies cancer in mutation carriers remains unclear. We used Mendelian randomization approaches to evaluate the association and BMI on risk, using data from Consortium Investigators Modifiers with 14 676 BRCA1 7912 BRCA2 carriers, including 11 451 cases cancer. created a genetic score 586 height-associated variants 93 BMI-associated variants....
Early age at onset of breast cancer (eoBC) is suggestive an increased genetic risk. Although testing offered to all eoBC-affected women, in isolated cases the detection rate pathogenic variants <10%. This study aimed assessing role constitutive promoter methylation BC-associated loci as underlying predisposing event women with eoBC and negative family history. Promoter 12 was assessed by MassARRAY technology blood from 154 BRCA1/2 patients history, 60 healthy controls. Hypermethylation...
Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic familial factors. About 50 common variants have been shown to modify BC carriers. All but three, were identified in general population studies. Other carrier-specific susceptibility may exist studies of so far underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 cases 13,007 with or mutations. identify robust associations 2 3 carriers, P < 10-8, at...
Abstract We report on the clinical and molecular characterization of eight patients, one male seven females, with diagnosis Cornelia de Lange syndrome (CdLS), who were found to carry distinct mutations SMC1A gene. Five are novel, two involving amino acid residues previously described as altered in a different way. The other three have been reported each single case. Comparison pairs individuals same mutation indicates only partial overlap their phenotypes. following novel missense mutations,...
BACKGROUND Male breast cancer (MBC) is a rare disease whose etiology appears to be largely associated with genetic factors. BRCA1 and BRCA2 mutations account for about 10% of all MBC cases. Thus, fraction cases are expected due factors not yet identified. To further explain the susceptibility MBC, whole‐exome sequencing (WES) targeted gene were applied high‐risk, BRCA1/2 mutation–negative METHODS Germ‐line DNA 1 male 2 female (BC) from pedigree showing first‐degree family history was...
Inherited mutations in BRCA1, and, mainly, BRCA2 genes are associated with increased risk of male breast cancer (MBC). Mutations PALB2 and CHEK2 may also increase MBC risk. Overall, these functionally linked to DNA repair pathways, highlighting the central role genome maintenance genetic predisposition. MUTYH is a gene whose biallelic germline variants cause MUTYH-associated polyposis (MAP) syndrome. Monoallelic have been reported families both colorectal there some evidence on women...
Cornelia de Lange syndrome (CdLS) is a rare, congenital characterized by growth retardation, dysmorphic face, mental retardation and limb reduction defects. Clinical manifestations of CdLS can be extremely variable. Mutations in NIPBL, SMC1A SMC3 genes, encoding for regulator two subunits the cohesin complex, respectively, are found 60-65% patients. We report on male with who mosaic c.2827delA mutation NIPBL gene. Allele quantitation pyrosequencing showed presence about 10% 33% DNA samples...