20 documents found, page 1 of 2

Diagnóstico molecular das síndromes de cancro hereditário da mama-ovário e colo...

Genetic testing for germline variants in homologous recombination repair genes,...

Homologous recombination repair (HRR) is the cellular mechanism for error-free repair of DNA double-strand breaks. Pathogenic germline variants in BRCA1 and BRCA2 lead to HRR deficiency associated with breast, ovarian, prostate, pancreatic cancers and are sensitive to PARP inhibitors (PARPi). Defects in HRR genes beyond BRCA1/2 could also result in HRR deficiency and sensitize the tumor to PARPi, thus expanding...

Reclassification of BRCA1/2 variants previously classified as VUS (ACMG-AMP gui...

In recent years, the number of BRCA1/2 germline variants associated with hereditary breast/ovarian cancer syndrome (HBOC), classified as variants of uncertain significance (VUS) according to ACMG-AMP guidelines (ACMGg) has been increasing. Reclassification of VUS as (likely) benign or (likely) pathogenic is crucial for maximizing diagnostic yield and appropriately managing HBOC patients. Recently, specific guid...

ABC system used as an add-on to clarify germline variants previously classified...

The increasing number of patients screened by NGS to identify germline variants associated with hereditary breast/ovarian cancer (HBOC) syndromes, is leading to a growing number of variants classified as Variants of Uncertain Significance (VUS) according to ACMG guidelines1. Since the ACMG system merges functional and clinical data into a one-dimensional system, it is not always clear how the classification was...

BRCA1 and BRCA2 variants identified in patients with a personal/familial histor...

Introduction: Screening for BRCA1 and BRCA2 variants (Vs) in patients with Hereditary Breast/Ovarian Cancer (HBOC) or other Hereditary Cancer Syndromes (HCS) is performed using next-generation sequencing (NGS), allowing detection of a high number and types of Vs. The growing use of PARP inhibitors (PARPi) in the treatment of patients with homologous recombination-deficient tumors contributes to an increasing nu...

Reporting of secondary findings in clinical genomic sequencing: national guidel...

Introduction: The rapid and growing integration of exome and genome sequencing into clinical genetic diagnosis raises awareness regarding the identification of variants of potential clinical value unrelated to the primary reason for testing (secondary findings, SF). SF pose major challenges, as multiple issues (medical, legal, ethical, economic) and different contexts (e.g. paediatric and prenatal diagnosis, pa...

Hereditary breast and ovarian cancer: two cases of double heterozigosity for pa...

Introduction: Hereditary breast and ovarian cancer (HBOC) is estimated to represent 5-10% of all breast and ovarian cancer cases. Pathogenic germline variants in BRCA1 and BRCA2 account for 25% of familial cases. The identification of genetic defects in HBOC patients allows detection of carriers that can benefit from cancer risk management protocols, and predictive genetic testing to at-risk family members, aft...

NGS Panels applied to Hereditary Cancer Syndromes

Cancer is among the leading causes of morbidity and mortality worldwide (Okur et al, 2017). Germline pathogenic variants for monogenic, highly penetrant cancer susceptibility genes are observed in 5%–10% of all cancers (Lu et al, 2014). Hereditary cancers due to monogenic causes are characterized by earlier age of onset, other associated cancers, and often a family history of specific cancers. From the clinical...

Presumed TP53 mosaicism: variants detected using a NGS hereditary cancer multig...

Aims/Context: NGS multigene panels are routinely used to identify germline pathogenic variants in cancer susceptibility genes. In addition, NGS allows the identification of low-level mosaicism events that may not be detectable by conventional Sanger sequencing. We describe two cases of presumed TP53 mosaic variants detected by NGS on blood-derived DNA, and confirmed by ARMS-PCR and Sanger sequencing. Case 1: fe...

Avaliação externa da qualidade e acreditação do diagnóstico molecular da altera...

A Qualidade no diagnóstico molecular em genética humana é uma presença constante na rotina da nossa Unidade. A participação em programas de Avaliação Externa da Qualidade (AEQ), nomeadamente no United Kingdom National External Quality Assessment Service for Leucocyte Immunophenotyping (UK-NEQAS LI), é fundamental para manter o laboratório atualizado a nível das recomendações sobre as boas práticas em diagnóstic...