Search results for " germline mutations"

showing 6 items of 6 documents

A possible role of FANCM mutations in male breast cancer susceptibility: Results from a multicenter study in Italy

2018

Abstract Introduction Breast cancer (BC) in men is a rare disease, whose etiology appears to be associated with genetic factors. Inherited mutations in BRCA1/2 genes account for about 10–15% of all cases. FANCM, functionally linked to BRCA1/2, has been suggested as a novel BC susceptibility gene. Our aim was to test if FANCM germline mutations could further explain male BC (MBC) susceptibility. Methods We screened the entire coding region of FANCM in 286 MBCs by a multi-gene panel analysis, and compared these data with available whole exome sequencing data from 415 men used as population controls. Moreover, we genotyped the two most frequent FANCM mutations (c.5101C>T and c.5791C>T) in 506 …

0301 basic medicineMaleMutation rateSettore MED/06 - Oncologia MedicaDNA Helicasemedicine.disease_causeBRCA1/2; Breast cancer susceptibility; FANCM; Germline mutations; Male breast cancer; Adult; Aged; Aged 80 and over; Biomarkers Tumor; Breast Neoplasms Male; Case-Control Studies; DNA Helicases; Genetic Predisposition to Disease; Genotype; Germ-Line Mutation; Humans; Italy; Male; Middle Aged; Risk Factors; Whole Genome Sequencing; Young Adult; Surgery0302 clinical medicineFANCMRisk Factorshemic and lymphatic diseasesGermline mutationGenotypeBRCA1/2; Breast cancer susceptibility; FANCM; Germline mutations; Male breast cancer; SurgeryFANCMMutation frequencyGeneticsAged 80 and overeducation.field_of_studyMutationGeneral MedicineMiddle AgedItaly030220 oncology & carcinogenesisMale breast cancerCase-Control StudieHumanAdultcongenital hereditary and neonatal diseases and abnormalitiesGenotypePopulationBreast Neoplasms Male03 medical and health sciencesYoung AdultGermline mutationBRCA1/2medicineBiomarkers TumorHumansGenetic Predisposition to DiseaseeducationGermline mutationsGerm-Line MutationAgedBreast cancer susceptibilityWhole Genome Sequencingbusiness.industryRisk FactorDNA Helicasesnutritional and metabolic diseasesmedicine.diseaseMale breast cancer030104 developmental biologyCase-Control StudiesSurgerybusiness
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Recommendations for the implementation of BRCA testing in the care and treatment pathways of ovarian cancer patients

2016

In the last 20 years, following the identification of the BRCA1 and BRCA2 genes (hereinafter referred to as the BRCA genes), preventive pathways have been developed for the identification and clinical management of individuals at high risk of developing breast and ovarian cancer due to the presence of a pathogenic variant in either of these genes. These pathways are aimed at educating high-risk subjects on programs targeted toward early diagnosis and cancer risk reduction. The approval of a novel class of drugs, the PARP enzyme inhibitors, for the treatment of ovarian cancer patients carrying high-risk BRCA pathogenic variants has changed this scenario. BRCA testing, in addition to providin…

0301 basic medicineOncologyCancer ResearchGenes BRCA2Genes BRCA1Brca testingBRCA1; BRCA2; genetic testing; germline mutations; ovarian cancer; PARP inhibitors; somatic mutations; Oncology; Cancer ResearchSettore MED/03 - GENETICA MEDICA0302 clinical medicineClinical decision makingInformed consentsomatic mutationBRCA1 BRCA2 genetic testing germline mutations somatic mutations ovarian cancer PARP inibitorsDisease management (health)PARP inhibitorsOvarian NeoplasmsTumorInformed Consentmedicine.diagnostic_testDisease ManagementGeneral MedicinePrognosisBRCA1; BRCA2; genetic testing; germline mutations; ovarian cancer; PARP inhibitors; somatic mutations; Biomarkers Tumor; Clinical Decision-Making; Disease Management; Female; Genes BRCA1; Genetic Variation; Germ-Line Mutation; Humans; Informed Consent; Mutation; Ovarian Neoplasms; Prognosis; Genes BRCA2; Genetic Testing; Oncology; Cancer Researchovarian cancergermline mutationOncology030220 oncology & carcinogenesisgermline mutationsFemaleHumanmedicine.medical_specialtyPrognosiClinical Decision-MakingMEDLINEgenetic testing03 medical and health sciencesPARP inibitorsInternal medicinemedicineBiomarkers TumorHumansGerm-Line MutationGenetic testingGynecologyBRCA1; BRCA2; PARP inhibitors; genetic testing; germline mutations; ovarian cancer; somatic mutationsbusiness.industryOvarian NeoplasmGenetic Variationmedicine.diseaseBRCA1BRCA2030104 developmental biologyPARP inhibitorGenesMutationsomatic mutationsOvarian cancerbusinessBiomarkers
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Recommendations for the implementation of BRCA testing in ovarian cancer patients and their relatives

2019

The current availability of new Poly(ADP-ribose) Polymerase (PARP)-inhibitors for the treatment of ovarian cancer patients independently of the presence of a BRCA pathogenic variant, together with the validation of somatic test for the analysis of BRCA1/2 genes, involves the need to optimise the guidelines for BRCA testing. The AIOM-SIGU-SIBIOC-SIAPEC-IAP Italian Scientific Societies, in this position paper, recommend the implementation of BRCA testing with 2 main objectives: the first is the identification of ovarian cancer patients with higher probability of benefit from specific anticancer treatments (test for response to therapy); the second goal, through BRCA testing in the family memb…

0301 basic medicineOncologyGenetic testingendocrine system diseasesSettore MED/03 - GENETICA MEDICAMedical OncologyBiochemistrychemistry.chemical_compound0302 clinical medicineGermline mutationPARP inhibitorsTrabectedinSocieties MedicalOvarian Neoplasmsmedicine.diagnostic_testBRCA1 ProteinHematologyfemale genital diseases and pregnancy complicationsOncologyItaly030220 oncology & carcinogenesisFemalemedicine.drugHumanmedicine.medical_specialtyGenetic counselingOlaparib03 medical and health sciencesGeneticSomatic mutationsOvarian cancerMedicalInternal medicineBRCA1; BRCA2; Genetic testing; Germline mutations; Ovarian cancer; PARP inhibitors; Somatic mutations; BRCA1 Protein; BRCA2 Protein; Biochemistry; Female; Genetic Testing; Genetics; Humans; Italy; Medical Oncology; Ovarian Neoplasms; Germ-Line Mutation; Societies MedicalGeneticsmedicineGenetic predispositionHumansRucaparibGermline mutationsGerm-Line MutationGenetic testingBRCA2 Proteinbusiness.industrySomatic mutationOvarian NeoplasmCancermedicine.diseaseBRCA1BRCA2BRCA1; BRCA2; Genetic testing; Germline mutations; Ovarian cancer; PARP inhibitors; Somatic mutations030104 developmental biologyPARP inhibitorchemistrySocietiesOvarian cancerbusiness
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Telomerase reverse transcriptase germline mutations and hepatocellular carcinoma in patients with nonalcoholic fatty liver disease

2017

Abstract In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases. The aim of this study was to examine telomere length and germline hTERT mutations as associated with NAFLD‐HCC. In 40 patients with NAFLD‐HCC, 45 with NAFLD‐cirrhosis and 64 healthy controls, peripheral blood telomere length was evaluated by qRT‐PCR and hTERT coding regions and intron–exon boundaries sequenced. We further analyzed 78 patients affected by primary liver cancer (NAFLD‐PLC, 76 with HCC). Enrichment of rare coding mutations (allelic frequ…

MaleCancer ResearchHepatocellular carcinomaSeverity of Illness IndexGermlineLoss of heterozygosityCohort StudiesLiver disease0302 clinical medicineNon-alcoholic Fatty Liver DiseaseNuclear Medicine and ImagingNonalcoholic fatty liver disease80 and overLeukocytesTelomeraseTelomere ShorteningOriginal ResearchCancer BiologyAged 80 and overHepatocellular carcinoma; Nonalcoholic fatty liver; Rare germline mutations; Telomerase reverse transcriptase; Telomere; Oncology; Radiology Nuclear Medicine and Imaging; Cancer ResearchtelomereLiver Neoplasmstelomerase reverse transcriptaseMiddle Aged3. Good healthPhenotypeOncology030220 oncology & carcinogenesisHepatocellular carcinoma030211 gastroenterology & hepatologyFemaleDisease SusceptibilityRadiologySequence AnalysisRare germline mutationCarcinoma HepatocellularMononuclearBiology03 medical and health sciencesGermline mutationHepatocellular carcinoma; Nonalcoholic fatty liver; Rare germline mutations; Telomerase reverse transcriptase; Telomere; Aged; Aged 80 and over; Alleles; Amino Acid Substitution; Carcinoma Hepatocellular; Cohort Studies; Computational Biology; Disease Susceptibility; Female; Genetic Association Studies; Humans; Leukocytes Mononuclear; Liver Neoplasms; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Phenotype; Sequence Analysis DNA; Severity of Illness Index; Telomerase; Telomere; Telomere Shortening; Germ-Line Mutationmedicinenonalcoholic fatty liverHumansRadiology Nuclear Medicine and imagingTelomerase reverse transcriptaseAllelesGenetic Association StudiesGerm-Line MutationAgedrare germline mutationsCarcinomaComputational BiologyHepatocellularDNASequence Analysis DNAmedicine.diseasedigestive system diseasesTelomereAmino Acid SubstitutionCancer researchLeukocytes MononuclearCancer Medicine
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Insight into genetic susceptibility to male breast cancer by multigene panel testing: results from a multicenter study in Italy

2019

Breast cancer (BC) in men is rare and genetic predisposition is likely to play a relevant role in its etiology. Inherited mutations in BRCA1/2 account for about 13% of all cases and additional genes that may contribute to the missing heritability need to be investigated. In our study, a well-characterized series of 523 male BC (MBC) patients from the Italian multicenter study on MBC, enriched for non-BRCA1/2 MBC cases, was screened by a multigene custom panel of 50 cancer-associated genes. The main clinical-pathologic characteristics of MBC in pathogenic variant carriers and non-carriers were also compared. BRCA1/2 pathogenic variants were detected in twenty patients, thus, a total of 503 n…

OncologyAdultMaleCancer Researchmedicine.medical_specialtyPALB2Adenomatous Polyposis Coli Proteinmale breast cancerGene mutationBreast Neoplasms MaleDNA GlycosylasesBRCA1/2; cancer susceptibility genes; germline mutations; male breast cancer; multigene panel testing03 medical and health sciencesYoung Adult0302 clinical medicinemultigene panel testingMUTYHMissing heritability problemBRCA1/2Internal medicinemedicineGenetic predispositionHumansGenetic Predisposition to Diseasecancer susceptibility genecancer susceptibility genesskin and connective tissue diseasesCHEK2Genetic Association StudiesAgedAged 80 and overbusiness.industryCase-control studySequence Analysis DNAMiddle Agedmedicine.diseaseCheckpoint Kinase 2germline mutationOncologyItaly030220 oncology & carcinogenesisMale breast cancerCase-Control StudiesMutationgermline mutationsbusinessFanconi Anemia Complementation Group N Protein
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Germline loss-of-function variants in the BARD1 gene are associated with early-onset familial breast cancer but not ovarian cancer

2019

Background The role of the BARD1 gene in breast cancer (BC) and ovarian cancer (OC) predisposition remains elusive, as published case-control investigations have revealed controversial results. We aimed to assess the role of deleterious BARD1 germline variants in BC/OC predisposition in a sample of 4920 BRCA1/2-negative female BC/OC index patients of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). Methods A total of 4469 female index patients with BC, 451 index patients with OC, and 2767 geographically matched female control individuals were screened for loss-of-function (LoF) mutations and potentially damaging rare missense variants in BARD1. All patients met the …

OncologyGermline0302 clinical medicineLoss of Function MutationSurgical oncologyOdds RatioPrevalenceMissense mutation030212 general & internal medicineAge of Onset10. No inequalityExomeEarly onset breast cancerAged 80 and overOvarian NeoplasmsBARD1 GeneHigh-Throughput Nucleotide SequencingMiddle Agedlcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens3. Good health030220 oncology & carcinogenesisFemaleTechnology PlatformsResearch ArticleAdultmedicine.medical_specialtyAdolescentUbiquitin-Protein Ligases610Breast Neoplasmslcsh:RC254-282Young Adult03 medical and health sciencesGermline mutationBreast cancerOvarian cancerInternal medicinemedicineBARD1HumansGenetic Predisposition to DiseaseGermline mutationsGenetic Association StudiesGerm-Line MutationAgedbusiness.industryTumor Suppressor ProteinsOdds ratiomedicine.diseaseConfidence intervalBARD1; Early onset breast cancer; Germline mutations; Ovarian cancerOvarian cancerbusiness
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