Molecular detection of known and novel cancer predisposition genes

Diagnosis of inherited cancer susceptibility has implications for both the patient and their family, as certain drugs may be more effective in cancers caused by a patient’s inherited cancer risk. Carrier testing can also determine whether family members are at risk of cancer. Both the patient and at-risk family members may benefit from increased screening, surveillance and/or prophylactic cancer prevention measures. However, current gene-by-gene testing strategies are costly and time consuming.

To try to speed diagnosis, Dr. Schrader will use cutting-edge DNA sequencing technologies to identify the inherited basis of cancers that run in families or occur multiple times in a single individual. Dr. Schrader will also test the patient’s tumor DNA alongside their normal DNA to look for candidate genes altered in both samples that are most likely to be the basis of the patient’s inherited cancer.

As part of her five-year research program, Dr. Schrader also proposes using these same sequencing technologies to test whether we can improve upon current cancer detection strategies in individuals with known cancer susceptibilities. By screening body fluids for free DNA released from early tumors with secondary mutations, it may be possible to detect evidence of early tumors. A positive screen may alert physicians to undertake more targeted diagnostic strategies to find and treat cancers at an early stage. Furthermore, if these technologies are successful in detecting early cancer in these high-risk patient groups, similar strategies could also be considered for screening for common types of cancer in the general population. Finally, genome-wide sequencing also has the potential to reveal information regarding non-cancer related genetic disease risks. Arguably, the clinical uptake of genome-wide sequencing has been the fastest in oncology, where tumor sequencing is undertaken to identify drug-targetable mutations. Clinical and research practices regarding the management of potentially clinically significant incidental genomic findings are evolving. As a medical geneticist in the BC Cancer Agency, Dr. Schrader will research both the cancer and non-cancer related incidental findings revealed through the course of clinical and research tumor sequencing.

Understanding of the scope of potential incidental findings will be critical as the policy and practice moves forward with this regard.