Analysis of rare disruptive germline mutations in 2135 enriched BRCA-negative breast cancers excludes additional high-impact susceptibility genes.

Background: Breast cancer has a significant heritable basis, of which ∼60% remains unexplained. Testing for BRCA1/BRCA2 offers useful discrimination of breast cancer risk within families, and identification of additional breast cancer susceptibility genes could offer clinical utility.

Patients And Methods: We included 2135 invasive breast cancer cases recruited via the Breast and Ovarian Cancer Susceptibility study, a retrospective UK study of familial breast cancer.

Evaluation of Cancer-Based Criteria for Use in Mainstream BRCA1 and BRCA2 Genetic Testing in Patients With Breast Cancer.

Importance: Increasing BRCA1 and BRCA2 (collectively termed herein as BRCA) gene testing is required to improve cancer management and prevent BRCA-related cancers.

Objective: To evaluate mainstream genetic testing using cancer-based criteria in patients with cancer.

Design, Setting, And Participants: A quality improvement study and cost-effectiveness analysis of different BRCA testing selection criteria and access procedures to evaluate feasibility, acceptability, and mutation detection performance was conducted at the Royal Marsden National Health Service Foundation Trust as part of the Mainstreaming Cancer Genetics (MCG) Programme.

Identification of new Wilms tumour predisposition genes: an exome sequencing study.

Background: Wilms tumour is the most common childhood renal cancer and is genetically heterogeneous. While several Wilms tumour predisposition genes have been identified, there is strong evidence that further predisposition genes are likely to exist. Our study aim was to identify new predisposition genes for Wilms tumour.

The ICR639 CPG NGS validation series: A resource to assess analytical sensitivity of cancer predisposition gene testing.

The analytical sensitivity of a next generation sequencing (NGS) test reflects the ability of the test to detect real sequence variation. The evaluation of analytical sensitivity relies on the availability of gold-standard, validated, benchmarking datasets. For NGS analysis the availability of suitable datasets has been limited.

The Quality Sequencing Minimum (QSM): providing comprehensive, consistent, transparent next generation sequencing data quality assurance.

Next generation sequencing (NGS) is routinely used in clinical genetic testing. Quality management of NGS testing is essential to ensure performance is consistently and rigorously evaluated. Three primary metrics are used in NGS quality evaluation: depth of coverage, base quality and mapping quality.

CoverView: a sequence quality evaluation tool for next generation sequencing data.

Quality assurance and quality control are essential for robust next generation sequencing (NGS). Here we present CoverView, a fast, flexible, user-friendly quality evaluation tool for NGS data. CoverView processes mapped sequencing reads and user-specified regions to report depth of coverage, base and mapping quality metrics with increasing levels of detail from a chromosome-level summary to per-base profiles.