Analysis Of Full-length Transcripts For Variant Classification In Breast Cancer

The future of successful genetic screening in New Zealand requires increased sensitivity and specificity of tests, and informed clinical management for high-risk breast cancer families.  

To date a lot of attention has gone on BRCA1/2 and that focus remains, however for this study the focus is on other high-risk breast cancer genes which currently do not reliably have the specificity that we need as we often identify variants of unknown significance. Using the latest technology (nanopore sequencing – a world first) which involves splicing the full length of the isoforms for BARD1, CDH1, CHEK2, PTEN, PALB2 and TP3, we expect to more reliably identify the necessary mutations. This will ensure that clinicians, the individuals affected and their families will be more likely to be able to take actions to reduce the likelihood of developing disease. How – through better surveillance techniques, treatments, surgery all in the hope of reducing the risk of advanced breast cancer. Two of the research team are members of an international expert panel ( who have been charged with developing rules for doctors so they can interpret genetic results. It is because of these linkages that their findings will be applied within clinical diagnostic settings around the world.

Identification of cancer-causing mutations in breast cancer susceptibility genes has well-defined and actionable implications for disease prevention. Of added value, outcomes from this research will also be integrated into international guidelines and as a result people globally will benefit. In the future this work can be extended to moderate and high-risk genes and also to better understand potential differences across Maori and Pasifika for whom there are currently no reliable norms.

HOST INVESTIGATOR: The University of Otago