[Detecting Large Germline Rearrangements of BRCA1 by Next Generation Tumor Sequencing]
A Minucci1,2, G Mazzuccato1, C Marchetti3,4
1Molecular Diagnostic and Genomics Laboratory, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, 00168 Italy.
Molekuliarnaia Biologiia
|August 26, 2020
Summary
Next-generation sequencing (NGS) can accurately detect large genomic rearrangements (LGRs) in BRCA1 genes within tumor tissues. This validates NGS for identifying BRCA1 LGRs in primary tumors, crucial for hereditary cancer diagnostics.
Area of Science:
- Genomics
- Oncology
- Molecular Diagnostics
Background:
- Pathogenic variants (PVs) in BRCA1/2 genes are common causes of hereditary breast and ovarian cancer.
- While single nucleotide variants are frequent, large genomic rearrangements (LGRs) also contribute significantly to BRCA-related hereditary cancers.
- Detecting LGRs is essential when sequencing fails to identify PVs in hereditary cancer families.
Purpose of the Study:
- To validate Next-Generation Tumor Sequencing (NGTS) for detecting BRCA1 large genomic rearrangements (LGRs) in surgical tumor tissue.
- To assess the feasibility of using tumor samples for germline LGR (gLGR) detection.
- To establish NGS as a reliable method for identifying BRCA1 LGRs directly from tumor specimens.
Main Methods:
- Utilized Next-Generation Tumor Sequencing (NGTS) technology.
- Analyzed quantitative sequencing reads with bioinformatics tools to detect structural variations.
- Focused on detecting seven known BRCA1 gLGRs in high-grade serous ovarian cancer (HGSOC) patient tumor samples.
Main Results:
- Successfully detected seven distinct BRCA1 gLGRs in primary tumor samples from HGSOC patients.
- Demonstrated the accuracy of NGS in identifying BRCA1 gLGRs directly from tumor tissue.
- Confirmed that NGS can identify germline LGRs in tumor samples, even when they are not detectable in blood.
Conclusions:
- NGS technology is effective for detecting BRCA1 gLGRs in primary tumor tissues.
- Evaluating BRCA1 LGRs from tumor samples using NGS is a viable alternative to blood testing, especially when tumor-based screening is initiated.
- NGS sequencing of tumor samples holds promise for detecting both somatic and germline LGRs in BRCA genes.
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