Hereditary cancers: a complex and challenging field
Detecting hereditary cancer still poses significant challenges for laboratories worldwide. Germline cancers are defined as those caused by inherited genetic variants within cancer susceptibility genes and account for 5-10% of all cancer cases,2 including breast, ovary, uterus, prostate, and cancers of the gastrointestinal system.
While molecular genetic testing can be used to determine if individuals carry specific inherited genetic variants, interpreting and effectively communicating test results present further complexities.
One of the primary hurdles is the complexity and diversity of cancer-related genes and mutations. Identifying specific genetic alterations requires advanced technologies and expertise, as well as access to comprehensive genetic databases for accurate interpretation. Additionally, the high cost of genetic testing and the limited availability of specialized laboratories pose financial and logistical challenges.
For example, gene alternations within BRCA1 and BRCA2 are known to increase susceptibility to breast, ovarian and prostate cancer, and this affects 1 in 300-400 people.3 However, BRCA1 contains many repetitive sequences and has high GC content, making it prone to sequencing errors and alignment artifacts, increasing the likelihood of false-positive or -negative results, compromising the accuracy of testing.
The BRCA genes are not the only cancer risk genes; there are now over 100 genes recognised to enhance the risk of developing cancer and each gene can present hundreds of variants, making interpretation a challenge for any testing provider.
Additionally, each year Genomic directories, such as the National Genomic Test Directory UK are updated to include new targets. Recent updates to the NGT directory have seen the addition of 5 new genes: REST, DLST, SLC25A11, RNF43 and MDH2, which have an association to inherited cancer syndromes. The everchanging legislations, makes it difficult for genomic testing service laboratories to stay up to date as commercial kit providers are struggling to include all the clinically relevant targeted content in their products.