Whole-genome sequencing successfully identifies cancer-related mutations

A first of its kind study has used whole-genome sequencing to evaluate a series of genomes from 258 cancer patients in the hope of improving our ability to diagnose cancer predisposing mutations.

Using whole-genome sequencing techniques, physicians and genetic counselors at the University of Texas Southwestern Medical Center (TX, USA) currently help patients assess their risk for multiple cancer types. If a known genetic predisposition is identified, the team counsels the patient regarding best practice for early cancer detection and prevention.

In this study, researchers developed new methods for analysis of the large amounts of data generated by whole-genome sequencing. Specifically, the researchers, led by Theodora Ross (UT Southwestern), devised a method to allow comparison of groups of patients with BRCA1/2 mutations with a group without such mutations. All expected BRCA1/2 mutations were identified, with at least 88.6% detected with confidence. In contrast, non-BRCA oncogene mutations were observed in the other cohort.

“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,” explained Ross. “Mystery patients are those who have a strong family history for cancer but after standard genetic testing, no genetic diagnoses are made. In our study, sequencing allowed us to discover novel candidate cancer gene mutations in mystery patients.”

The researchers have, however, acknowledged that further investigation will be needed in order to interpret the precise clinical implications of the mutations found using their method.

Sources: Foley S, Rios J, Mgbemena V. Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic. EbioMedicine doi:10.1016/j.ebiom.2014.12.003 (2014) (Epub ahead of print); UT Southwestern Medical Center News Release