Pitfalls and Caveats in BRCA Sequencing

摘要: Between 5 and 10% of breast cancer cases are considered to result from hereditary predisposition. Germ-line mutations in BRCA1 BRCA2 responsible for an inherited predisposition ovarian cancer. Direct nucleotide sequencing is the gold standard technique mutation detection genes such as BRCA2. In many laboratories that analyze BRCA2, previous direct sequencing, screening techniques identify sequence variants PCR amplicons performed. The detected these may be frameshift (insertions or deletions), nonsense mutations, missense mutations. clinical interpretation cause disease difficult establish case Only 30-70% families which a component suspected, and/or detected. Negative results due to: wrong selection proband; regulatory portion genes; gene silencing epigenetic phenomena; large genomic rearrangements produce deletions whole exons. Another possibility explains lack alterations presence undiscovered interact with low-penetrance genes, like CHEK2.