For many years, targeted genetic screening of the BRCA1 and BRCA2 genes was the basic genetic test in hereditary breast and ovarian cancer. These two genes confer an appreciable risk for breast cancer, but recent studies have identified new genes which are also associated with increased risk for breast cancer. Specifically, between 15 to 20 genes have been associated with an additional risk of up to 20% for hereditary breast cancer, and some of these genes are also associated with increased risk for other cancers, such as pancreatic cancer, ovarian cancer and sarcomas. For example, the BARD1, BRIP1, NBN, RAD50 and RAD51C genes are involved in the DNA repair mechanism (Fanconi anemia-BRCA pathway) through interactiion with the BRCA1 and BRCA2 genes, and as a result mutations in these genes confer a 4-5 times increased risk for breast cancer. Therefore, mutation detection through parallel-simultaneous analysis of multiple genes (including the BRCA1 and BRCA2 genes), is estimated to result in a 5-10 fold increase in the risk assessment for breast and ovarian cancer. In the vast majority of cases the mode of inheritance is autosomal dominant, with variable expressivity and penetrance, meaning that a person with a mutation in one of these genes will not necessarily develop the disease or will develop varying clinical symptoms and disease severity.
he understanding of the genetic contribution to hereditary breast and ovarian cancer, provides us with very useful information about disease progression and family risk, which may vary depending on the precise molecular diagnosis. Knowing that a person is at an increased risk will help in effective medical management, including regular monitoring and specific actions to reduce the risk of developing the disease.
The recent introduction of massive parallel sequencing through Next Generation Sequencing technology (NGS) has nowadays become a highly effective diagnostic strategy, permitting the parallel analysis of a large number of genes involved in the expression of breast and ovarian cancer.
InterGenetics has developed and offers an NGS panel for the genomic analysis of 19 genes (AR, ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, DIRAS3, ERBB2, NBN, PALB2, PTEN, RAD50, RAD51, STK11, TP53, CASP8, TGFB1) in which mutations have been linked to breast and ovarian cancer.
We perform DNA sequence analysis, via Next Generation Sequencing (NGS) on a Genome Analyzer – Ion Proton platform, of all exons and intron-exon junctions/splice sites of the 19 genes, allowing us to detect >98% of all pathogenic mutations of the genes through the use of specially developed bioinformatics tools.
Where possible and/or necessary, we carry out additional MLPA analysis in order to detect deletions/duplications of the genes (please consult the final test report).
The test is highly sensitive and complex, so it is necessary that the results are assessed by a specialized team of clinical and molecular geneticists, in order to ensure safe and reliable testing.
Proper clinical genetic assessment and genetic counseling, both before and after testing, is essential in order to determine the optimum testing strategy and also to communicate properly the concepts of pathological and normal.