UT Southwestern Medical Center cancer researchers have demonstrated that whole-genome sequencing can be used to identify patients’ risk for hereditary cancer, which can potentially lead to improvements in cancer prevention, diagnosis, and care. Their study, published online in the journal EBioMedicine, used whole-genome sequencing to evaluate a series of 258 cancer patients’ genomes to improve the ability to diagnose cancer-predisposing mutations.
About five percent to 10 percent of all cancers are caused by known inherited gene mutations, passed down from generation to generation. Mutations in the BRCA1 and BRCA2 genes are the most common cause of hereditary breast cancer. BRCA gene mutations are best known for their breast cancer risk, but they also cause increased risk for ovarian, prostate, pancreatic, and other cancers. In addition, there are many different genes, including ATM, CDH1, CHEK2, PALB2, PTEN, and TP53, that are associated with an increased risk for breast cancer, and researchers continue to discover additional genes that may affect cancer predisposition.
In this study, researchers developed new methods to analyze the large amount of data generated by whole-genome sequencing. Specifically, the team devised a method to compare a group of patients with BRCA1 or BRCA2 mutations to a group of patients without BRCA mutations. All expected BRCA1 and BRCA2 mutations were detected in the BRCA group, with at least 88.6 percent of mutations confidently detected. In contrast, different cancer gene mutations were found in the cohort without BRCA mutations.
“The results demonstrate that whole-genome sequencing can detect new cancer gene mutations in non-BRCA ‘mystery’ patients, demonstrating the added value whole-genome sequencing brings to the future cancer clinic,” says co-author Theodora Ross, MD, PhD. Further investigation is needed in order to be able to interpret the precise clinical implications of the mutations found.
Read the article at the EBioMedicine website
