Last month, the Cancer Research Institute (CRI) invited Corrie Painter, Ph.D., and Eliezer Van Allen, M.D., to discuss new advances in genetics and genomics in cancer patient care. These colleagues at the Broad Institute of MIT and Harvard offer a unique set of patient, scientific, and medical perspectives on what genes reveal about cancer risk and behavior. Both an angiosarcoma survivor and scientist, Dr. Painter leads patient-driven research projects to accelerate the discovery of new therapies. As both a computational biologist and medical oncologist, Dr. Van Allen has specific expertise in the analysis and interpretation of genomic data in treatment decisions.
During a special Cancer Immunotherapy Month live webinar, Drs. Painter and Van Allen fielded questions from cancer patients around the world—more than could be addressed within the hour. CRI spoke with Drs. Painter and Van Allen after the webinar to address a number of questions from our community.
Question: Why is there discordance between liquid biopsy results from the same person run at different labs?
Drs. Painter and Van Allen: There are a few reasons that one may see different results between different labs. First, the samples themselves may actually be different. Not every cancer cell has the exact same set of mutations. So when you draw blood that has DNA from cancer cells mixed in with the plasma, different days may show DNA from different groups of cells that have different mutations. Second, the way the tests are designed and interpreted is not the same between different companies. There is variability in how these tests are developed which may lead to differences in what they show.
Question: If genomic testing does not identify any mutations for which there are available targeted therapies, is there any value in evaluating drugs that target other genes on that pathway?
Drs. Painter and Van Allen: This is a great question. The short answer is we don’t know, though there are studies underway that are attempting to address these concepts and determine whether it might help to consider drug targets in terms of pathway actions (rather than directly on the genes).
Question: I have epithelioid hemangioendothelioma sarcoma. I had over 500 mutations screened with UCSF500 genomic panel and no mutations were found. What should I do now?
Drs. Painter and Van Allen: If you are interested in more expanded testing, there are commercial vendors that offer larger sequencing (e.g., whole exome, whole genome, whole transcriptome sequencing).
Question: Is anyone looking at folks who have Lynch syndrome or LiFraumeni who don't get cancer?
Drs. Painter and Van Allen: This is an important area of research. At Count Me In, we are gearing up to send questionnaires to several thousand cancer patients in order to understand their family history of cancer as well as familial disorders. We are hoping to develop research questions around people with hereditary disorders such as these.
Question: How is a gene fusion/translocation similar to or dissimilar to a genetic mutation?
Drs. Painter and Van Allen: A gene fusion is a rearrangement of the DNA between two genes, whereas a genetic mutation is a change in the DNA within one gene. Using the words “End Cancer” for an analogy, a fusion would be a fusion of the words to get something like “Encer” or “Caned” or any other combination of the two words. A mutation would be a change within one of the words “Eld Cancer,” for example. In both cases, the meaning of the word(s) can change.
Question: Will the genomic DNA change from one organ to another in case of metastasis? If the cancer metastasized from breast to lung, is one genomic testing sufficient?
Drs. Painter and Van Allen: So far we have learned that the genomic DNA does indeed change as tumors metastasize from the original organ to another site, although whether one needs to test both sites is unclear (and often not feasible for practical reasons). This may be where liquid biopsies (blood-based testing) may help, as this would in theory sample all of these sites at the same time, though studies are still needed to understand this phenomenon.
Question: For primary and metastatic tumors, cancer is usually defined by the organ in which it is discovered. Do you think that, one day, we will start defining cancers by genomic cell type rather than originating organ?
Drs. Painter and Van Allen: We aspire to exactly this goal!
Question: Can mitochondrial DNA play a role in cancer immunotherapy?
Drs. Painter and Van Allen: Great question. We don’t yet know, but studies are underway looking at this specifically.
Question: Can tracking longitudinal changes in tumor mutational burden be used to track response to therapy?
Drs. Painter and Van Allen: We and others are now investigating how we can track changes in genomics over time can help understand responses in real time.
Corrie Painter, Ph.D., an angiosarcoma survivor and former CRI Fellow, is associate director of operations and scientific outreach in the Cancer Program of the Broad Institute of MIT and Harvard. Dr. Painter also serves as the associate director of Count Me In, which launches patient-driven research projects across multiple cancer types, including the Angiosarcoma Project.
Eliezer Van Allen, M.D., is an assistant professor of medicine at Harvard Medical School, a clinician at Dana-Farber/Partners Cancer Care, and an associate member at the Broad Institute of MIT and Harvard. His research focuses on computational cancer genomics, the application of new molecular profiling technologies to advance precision cancer medicine, and studying resistance to cancer therapeutics.
CRI's "Cancer Immunotherapy and You" patient education webinar series is produced by the Cancer Research Institute and was hosted by Arthur Brodsky, Ph.D. Sponsorship for this webinar was generously provided by Bristol-Myers Squibb, Alkermes, and Foundation Medicine. Sponsorship does not influence editorial decisions or content. Browse our Cancer Immunotherapy and You Webinar Series playlist on YouTube or visit the Webinars page on our website to see other webinars in this series.
Image by Gerd Altmann from Pixabay