Next-generation sequencing bolsters breast, prostate and blood cancer research
Clayton R. Boldt, Ph.D.
MD Anderson’s Moon Shots Program™ was established to bring teams of world-class clinicians and researchers together in order to rapidly advance scientific discoveries into the clinic to save patients’ lives. Driving the work of the Moon Shots™ are 10 research platforms that provide unique expertise, technical support and novel infrastructure to the program’s 13 disease-focused initiatives.
One of those platforms is the Cancer Genomics Laboratory (CGL), which enables Moon Shots researchers to quickly analyze genetic information to learn as much as possible about a patients’ tumor. Maggi Morgan, scientific manager of the CGL, spoke with Cancer Frontline to share more about the work of the platform and how it supports the Moon Shots teams.
Q: Can you describe the CGL and its work with the Moon Shots Program?
A: The CGL platform is a next-generation sequencing laboratory working to drive discoveries that generate insights into the molecular basis of cancer. We provide data to clinical researchers that may inform personalized treatment strategies and has the potential to make a significant impact on the detection, management and treatment of cancer.
The CGL provides high-quality sequencing services to all of the Moon Shots teams. Next-generation sequencing is a tool that potentially allows researchers to discover significant functional mutations, genes and pathways that may be causally linked to cancer progression. Understanding the molecular basis for how tumors grow, metastasize and evolve is crucial because those discoveries may inform methods for early detection, personalized treatment and improved outcomes. To date, we have sequenced more than 7,500 samples across the 13 Moon Shots, resulting in more than 40 peer-reviewed publications.
Q: How does the platform contribute to MD Anderson’s mission of ending cancer?
A: Using next-generation sequencing, the CGL provides a powerful systematic mutation discovery vehicle. For example, by sequencing the DNA in a tumor before and after treatment, researchers hope to learn how cancer adapts to treatment and potentially becomes resistant to it. We are currently investigating this question for the Breast Cancer Moon Shot™.
This is how CGL helps to uncover the underlying molecular abnormalities that drive the growth and spread of cancer. As a result, we provide valuable data that may inform new avenues for targeted treatments, ultimately with the goal of making significant improvements in the lives of MD Anderson patients.
Q: How is the platform’s impact enhanced by collaboration?
A: The CGL collaborates with all Moon Shots and multiple platforms, including APOLLO (Adaptive Patient-Oriented Longitudinal Learning and Optimization) and the TRA (Translational Research Accelerator). While the CGL does not provide analytic services directly, we work alongside the bioinformatics analysis team to ensure data from multiple platforms are leveraged appropriately and deposited into the Enterprise Big Data Warehouse (EBDW).
Our bioinformatics group has developed sophisticated analytical tools that mine sequence data and translate it into results that are made available to the disease site teams for downstream analysis. Moreover, all Moon Shot™ data is deposited into the EBDW, becoming an institutional resource benefitting both patients and researchers.
Q: Which of your projects or achievements are you most proud of?
A: I interact directly with the disease site PI’s to develop proposals that are then reviewed and approved by Moon Shot leadership; so, I feel a personal connection to every project. That said, there are a couple of projects that I would like to highlight.
The HPV-Related Cancers Moon Shot™ is characterizing a rare HPV-related cancer with limited treatment options, especially for advanced disease. The team believes this to be the largest whole exome analysis of this cancer, with the potential to uncover the involvement of multiple cancer genes contributing to tumor development. The goal is to present results at the American Society of Clinical Oncology's Genitourinary Cancers Symposium in 2019.
The Myelodysplastic Syndromes and Acute Myeloid Leukemia Moon Shot™ has a study on clonal hematopoiesis of indeterminate potential (CHIP), defined as a pre-malignant condition in which somatic mutations are found in one or more leukemia-associated genes. Work from this team and others have found that individuals with CHIP carry a higher risk of developing hematological malignancies and an increased risk of developing therapy-related myeloid neoplasms (t-MNs). This work has been published by Dr. Koichi Takahashi and colleagues in Lancet Oncology and Blood Advances.
The next step is to use these findings to identify the patients at particularly high risk of developing t-MNs, and develop a strategy to mitigate the risk. The team is proposing a 10,000-patient study to understand the prevalence and prognostic significance of CHIP.
Q: Where do you see the platform in five years?
A: Within five years I think it is feasible that we will add liquid biopsies as a standard procedure to screen for early-stage cancers, monitor responses to treatment, and help explain why some cancers are resistant to therapies. Currently, the gold standard for getting high quality sequencing data is to use freshly biopsied tumor tissue, either frozen or formalin fixed. However, there is added risk and discomfort for patients. There has been a surge in research from the Prostate Cancer Moon Shot™ team, for example, to use circulating tumor DNA, which has the potential to enable full-tumor genome characterization collected by minimally invasive means.
Q: How has the Moon Shots Program made your work possible?
A: The CGL is unique in that we interact with every Moon Shot, which epitomizes the multidisciplinary team effort envisioned at the Moon Shots Program launch. Our work is made possible by the Moon Shot Program, and in return, we provide high-quality scientific and technical infrastructure, thus supporting and accelerating the research efforts of the disease sites. Further, the data generated by our platform is used to advance the work of Moon Shot teams and facilitate more collaborations with additional platform teams. Our collaboration with the Breast Cancer Moon Shot, for example, provided valuable insights into therapeutic targets, which they are now pursuing with the Center for Co-Clinical Trials.