Use of Treatment-Focused Tumor Sequencing to Screen for Germline Cancer Predisposition
This week we profile a recent publication in the Journal of Molecular Diagnostics from the lab of Dr. Aly Karsan (pictured, top, center of front row) at UBC and Canada’s Michael Smith Genome Sciences Centre with first author Tammy Lau (left).
Can you provide a brief overview of your lab’s current research focus?
There are two main areas of focus of my lab: The first is to understand the mechanisms of resistance and relapse in myeloid cancers, and find ways to target or bypass these resistance mechanisms; the second is to design and validate next-generation sequencing (NGS) assays that can be delivered to the clinic, as demonstrated by the current paper.
What is the significance of the findings in this publication?
We designed a next-generation sequencing assay to target genes that are relevant in both somatic and germline cancers. This assay can be applied to tumor tissue of cancer patients to detect variants that can inform their treatment options, while also screening for germline variants that result in hereditary cancer syndromes. Between 5 and 15% of cancers are thought to be directly related to germline variants in cancer predisposing genes. With confirmatory germline testing, this assay can identify at-risk families that may not have been eligible for genetic testing and allow these families to access screening for early detection of cancers. This work was entirely dependent on close collaborations with a number of dedicated individuals from the gynaecological oncology group (in particular Dr. Anna Tinker, Dr. Janice Wong and their respective teams) and the Hereditary Cancer Program (Drs. Intan Schrader and Sophie Sun and their team).
What are the next steps for this research?
We continue to develop and automate various clinical NGS assays. For instance we recently developed a whole transcriptomic assay for myeloid cancers (Nat Commun 2021), and we are working closely with the lymphoma group to develop assays for classification and ctDNA testing. Directly related to the current publication, we are part of a pan-Canadian consortium to develop ctDNA assays to predict early cancer development in carriers of germline mutations.