Researcher Interview: Matthew Meyerson
, by Amy E Blum, M.A.
Matthew Meyerson, M.D., Ph.D., Professor of Pathology at Dana-Farber Cancer Institute and Harvard Medical School, Director of the Center for Cancer Genome Discovery at Dana-Farber Cancer Institute, and Institute Member at the Broad Institute, spoke with Amy E. Blum, M.A., for this Researcher Interview.
Amy E Blum (AB): What is the major focus of your work in cancer genomics?
Matthew Meyerson (MM): The focus of my laboratory is understanding the genomic alterations that cause human lung cancer. Lung cancer is the leading cause of human cancer death, but the treatment of lung cancer has begun to be transformed by the discovery of actionable alterations in the cancer genome. Over the years my colleagues and I have discovered a number of prominent alterations in receptor tyrosine kinase genes, including mutation of the EGFR gene which is associated with response to treatment with the drugs erlotinib, gefitinib and afatinib. In the 2014 The Cancer Genome Atlas (TCGA) publication describing genomes of lung adenocarcinoma, the major subtype of lung cancer, we reported an expanded number of alterations in genes of the receptor tyrosine kinase/Ras/Raf pathway, including splice site mutations of the MET gene. Since that report, we are now starting to see examples of patients with mutations in the MET gene who are responding to treatment with crizotinib or other MET inhibitors. It has been very gratifying to see the clinical impact of some of our findings.
AEB: What are the top projects in your lab right now?
MM: Our biggest project is with TCGA on understanding somatic copy number alterations. We are providing the copy number analysis for each of the specific disease projects. For me the most exciting findings are providing evidence for unexpected similarity, or in some cases, distinction between different cancer types. For example, if we look at gynecological cancers, breast, ovarian, and endometrial cancers are considered to be quite different, but in fact, subtypes of these cancers have similar profiles when analyzed by copy number. A second example has been in the study of gastric carcinoma, which rather than bringing different cancer types together, has been a chance to identify subtypes. In that study we found that one subtype of stomach cancer associated with infection by the Epstein-Barr virus also shows amplification of genes whose function is to dampen the immune response. We can imagine that these amplifications could be dampening the immune response against the Epstein-Barr virus.
AEB: What are the latest results in your research on cancer and microbes?
MM: We know that there are cancers that are caused by infections and therefore are preventable by vaccination. The next issue is identifying undiscovered cancer-causing microbes. We have been very intrigued by our finding of an association between Fusobacterium and colon carcinoma that was also found by another TCGA associated group – Rob Holt’s group at the University of British Columbia. The jury is still out on the role of Fusobacterium in colon cancer – whether it is a cause, a consequence, or a coincidence – but it brings forward interesting hypotheses.
AEB: How do you envision the future of cancer genomics?
MM: I see it going a couple of ways. One is increasing the number and completeness of sequencing. For example, when my lab started sequencing, we were able to sequence a tiny fraction of the genome. Now we can sequence the whole genome and really start to understand the alterations. I anticipate that these technologies will continue to advance over the next years and we will be able to sequence whole genomes of many thousands of cancers. This will allow us to discover the many cancer genes that we do not yet know. Also, we will be able to start identifying alterations associated with cancer development, which will allow us to treat cancers we currently can’t see, for example, the precursors of certain cancers.
Second, the technology is moving towards being able to sequence the genomes of single cancer cells. If we can sequence a single cancer cell, [we can ask], “Is the cancer homogenous? Is it heterogeneous? Can we purify out the cancer cells from the normal cells?” I think this is incredibly powerful and improved sequencing technology will allow us to see a lot more.
AEB: What are the biggest challenges for the field of cancer genomics going forward?
MM: The first is the challenge of accurately interpreting the data. The first piece to this is actually finding the alterations of cancer genomes and the second is trying to ascertain which of these alterations are biologically important in the development of the cancer. This is going to involve both analytic approaches on cancer genomes and functional experiments in model systems. Our analytic and interpretative abilities are lagging behind our experimental abilities, so the challenge is developing these analytical approaches.
A second set of challenges is related to how we transfer cancer genome knowledge to clinical practice and how we use it in cancer diagnosis. To address this, we need to work on correlating the growing amount of cancer genome data with responses to therapy. For me, these are the major challenges going forward.
AEB: You have been involved in TCGA and are also a principal investigator at Harvard Medical School. How do you think that these types of collaborations fit into the broader landscape of science today?
MM: There are unique areas in research where these kinds of large consortia can be useful, [especially] in the generation and annotation of large data sets. It will be important to build on those areas of science where the big science model will be very useful, but the same time we do not want to extend the model too far. I think there is an enormous amount to be said for the creativity of the investigator-driven approach
AEB: What has team science meant to you and to the field of cancer genomics?
MM: It has been great to be part of TCGA and to be part of a big network. [TCGA] has brought together a wonderful community of scientists who have had the opportunity to work and contribute together. It has been an opportunity for all of us to really improve our technical abilities, and to improve our intellectual understanding of cancer; it’s given us the opportunity to really look across the big spectrum of cancer. The community-building aspect of TCGA has been a huge positive influence on the cancer research community and on the clinical application of genome discovery.