GTS5:BRCA-related cancer predisposition syndrome (BRCA1, BRCA2): Difference between revisions
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==Genetic Diagnostic Testing Methods== | ==Genetic Diagnostic Testing Methods== | ||
Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span> | Put your text here <span style="color:#0070C0">(''Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.'')</span> | ||
Germline diagnosis of ''BRCA1'' and ''BRCA2'' associated hereditary cancer predisposition is established by molecular genetic testing performed on constitutional DNA (e.g., blood or saliva). Testing strategies must detect both sequence variants and copy number alterations, as pathogenic variants span multiple variant classes. | |||
'''Primary testing approaches:''' Next-generation sequencing (NGS), including multigene hereditary cancer panels or genome/exome sequencing, is the first-line method for detection of single-nucleotide variants (SNVs), small insertions/deletions, and splice-site variants in ''BRCA1'' and ''BRCA2''. Copy-number variant (CNV) analysis, performed using NGS-based CNV calling, multiplex ligation-dependent probe amplification (MLPA), or array-based methods, is required to detect large genomic rearrangements, including multi-exon deletions or duplications, which represent a clinically significant subset of pathogenic variants. | |||
'''Supplementary and confirmatory methods:''' MLPA or other targeted deletion/duplication assays are commonly used to confirm suspected CNVs or when sequencing-only approaches are insufficient. Sanger sequencing may be employed for targeted variant confirmation or cascade testing in at-risk relatives once a familial pathogenic variant has been identified. | |||
'''Tumor testing:''' Tumor sequencing may identify somatic ''BRCA1/BRCA2'' alterations, loss of heterozygosity, or reversion mutations, which have implications for therapeutic selection and resistance, particularly in the context of PARP inhibitor therapy. Identification of a pathogenic ''BRCA1/BRCA2'' variant in tumor tissue should prompt confirmatory germline testing to distinguish hereditary from purely somatic events. | |||
==Additional Information== | ==Additional Information== | ||
Put your text here | Put your text here | ||