BRCA gene mutations in cancer

Differential Remodeling of the BRCA1 Interactome by a Unique Minimal Clinical Truncation Mutation

The paper identifies how the BRCA1-Y1853ter mutation alters protein interactions and cellular processes, suggesting gain-of-function effects in cancer.

Validation of a guidelines-based digital tool to assess the need for germline cancer genetic testing

The paper validates a digital tool for assessing germline cancer genetic testing eligibility based on patient and family history, showing high agreement with genetic counselors.

Two founder variants account for over 90% of pathogenic BRCA alleles in Orkney and Shetland

The paper identifies two founder BRCA variants in Orkney and Shetland populations, accounting for 93.5% of pathogenic BRCA alleles.

BRCA-DIRECT digital pathway for diagnostic germline genetic testing within a UK breast oncology setting: a randomised, non-inferiority trial

This study compares digital and in-person genetic counseling for germline testing in breast cancer patients, finding higher uptake with digital information without compromising other outcomes.

A workflow for clinical profiling of BRCA genes in Chilean breast cancer patients via targeted sequencing

The paper develops a Nextflow pipeline for BRCA1/2 variant detection in Chilean breast cancer patients using targeted sequencing and variant callers, identifying one pathogenic variant among 16 samples.

A Comprehensive and Accessible Model for Co-Segregation Analysis in BRCA1, BRCA2, and PALB2 Variant Classification

CAL-Leiden is a co-segregation model for BRCA1, BRCA2, and PALB2 variant classification, integrating population data and cancer types to improve pathogenicity assessment.

Evidence-based recommendations for gene-specific ACMG/AMP variant classification from the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel

The paper refines ACMG/AMP variant classification criteria for BRCA1 and BRCA2 by calibrating evidence strength and improving classification consistency through expert panel review.

Towards Personalized Breast Cancer Risk Management: A Thai Cohort Study on Polygenic Risk Scores

This study evaluates 140 breast cancer PRS models in a Thai population, identifying PGS004688 as the best-performing model with significant risk stratification.

BOADICEA model: updates to the BRCA2 breast cancer risks for ages 60 years and older

The paper updates breast cancer risk estimates for BRCA2 carriers aged 60 and older using data from two large studies.

Limitations in next-generation sequencing-based genotyping of breast cancer polygenic risk score loci

This study evaluates the accuracy of next-generation sequencing in capturing allele frequencies for polygenic risk score loci in breast cancer, finding significant deviations affecting risk prediction.

Meta-Analysis of Breast Cancer Risk for Individuals with PALB2 Pathogenic Variants

This paper performs a meta-analysis of breast cancer risk associated with PALB2 pathogenic variants, finding an overall risk of 12.80% by age 50 and 48.47% by age 80.

Real-world evaluation of deep learning algorithms to classify functional pathogenic germline variants

This study evaluates deep learning models for classifying pathogenic germline variants in hereditary breast cancer using UK Biobank data, finding limited clinical utility for variants of uncertain significance.

Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk

This study identifies seven novel genetic loci associated with high-grade serous ovarian cancer risk using a large-scale GWAS and develops polygenic scores for improved risk prediction.

A missense variant effect map for the human tumour suppressor protein CHK2

The paper creates a functional map of all possible missense variants in CHK2 to assess their impact on cancer risk.

Hereditary breast cancer next-generation sequencing (NGS) panel evaluation in the south region of Brazil: a novel BRCA2 candidate pathogenic variant is reported.

The paper evaluates a next-generation sequencing panel for hereditary breast cancer in a Brazilian population, identifying two pathogenic variants and one novel candidate pathogenic variant in BRCA2.

Tumor suppressor heterozygosity and homologous recombination deficiency mediate resistance to front-line therapy in breast cancer

The paper identifies how germline and somatic mutations interact to cause resistance to CDK4/6 inhibitors in breast cancer and proposes a sequential treatment strategy using PARP inhibitors.

Combining rare and common genetic variants improves population risk stratification for breast cancer

This study evaluates genetic screening approaches for breast cancer risk, finding that combining rare and common variants improves risk stratification.

AVENGERS: Analysis of Variant Effects using Next Generation sequencing to Enhance BRCA2 Stratification

The paper develops AVENGERS, a method using CRISPR-Cas9 to classify BRCA2 variants as functional or nonfunctional, improving the interpretation of variants of uncertain significance.

Saturation genome editing-based functional evaluation and clinical classification of BRCA2 single nucleotide variants

The paper functionally characterizes BRCA2 variants using saturation genome editing and classifies them clinically, finding functionally abnormal variants are associated with increased cancer risk.

Impact of genetic counselling strategy on diagnostic yield and workload for genome sequencing-based tumour diagnostics

This study evaluates genetic counselling strategies for genome sequencing-based tumour diagnostics, finding that post-test strategies reduce unnecessary referrals while maintaining PGV detection rates.

Multi-scale characterisation of homologous recombination deficiency in breast cancer

The paper develops methods to classify homologous recombination deficiency in breast cancer using mutational and transcriptional signatures, showing heterogeneity and single-cell microenvironment interactions.

Investigation of BRCA1 exon 11 genetic variations in breast cancer among Libyan women

The paper analyzes BRCA1 exon 11 genetic variations in Libyan breast cancer patients with a family history of cancer, identifying 12 variants, three of which are novel.

Influence of family history on penetrance of hereditary cancers in a population setting

The paper examines how family history affects cancer penetrance in individuals with pathogenic variants, finding higher risks with family history for BRCA1/2 and Lynch syndrome.

Prenatal BRCA1 epimutations contribute significantly to triple-negative breast cancer development

The paper identifies prenatal BRCA1 epimutations as a cause of approximately 20% of triple-negative breast cancers and low-ER expression breast cancers.

Development and evaluation of a novel educational program for providers on the use of polygenic risk scores

This paper evaluates an educational program for healthcare providers on polygenic risk scores, finding it improves their attitudes, confidence, knowledge, and preparedness for using PRS in clinical practice.

HRD-One: CLINICAL VALIDATION AND PERFORMANCE ASSESSMENT. Comparison between Myriad's myChoice(R), SOPHiA GENETICS SOPHiA Homologous Recombination Solution(R) and AmoyDx HRD Focus Panel(R)

HRD-One provides a reproducible HRD score with high concordance to myChoice(R) and identifies HRD in ovarian cancer samples with and without BRCA1/2 mutations.

Clinical case study meets population cohort: Identification of a BRCA1 pathogenic founder variant in Orcadians

The paper identifies a BRCA1 founder variant in Orcadians and estimates its high prevalence, suggesting population screening for this variant.

Variant-specific Mendelian Risk Prediction Model

The paper extends Mendelian risk prediction models to incorporate variant-specific penetrances, improving cancer risk predictions for BRCA1/2 pathogenic variants.

Whole exome sequencing and replication for breast cancer among Hispanic/Latino women identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer.

Incorporating alternative Polygenic Risk Scores into the BOADICEA breast cancer risk prediction model

This paper evaluates methods to incorporate alternative polygenic risk scores into the BOADICEA breast cancer risk prediction model, finding that retrospective likelihood approaches provide more accurate estimates.