Contributing to Tumor Molecular Characterization Projects with a Global Impact

My name is Nicholas Griner and I am the Scientific Program Manager for the Cancer Genome Characterization Initiative (CGCI) in the Office of Cancer Genomics (OCG). Until recently, I spent most of my scientific career working in a cancer research laboratory. In my postdoctoral training, my research focused on identifying novel pathways that contribute to both prostate and breast cancers and studying proteins within these pathways that may be targeted with cancer drugs. As my postdoctoral fellowship came to a close, I decided to pursue a position at the interface between research and clinical outcomes with more direct applications towards treating cancer patients. A job opening in OCG offered me this unique opportunity, and I started my position in December 2013. As CGCI program manager, I oversee two major molecular characterization projects: the Burkitt Lymphoma Genome Sequencing Project (BLGSP) and the HIV+ Tumor Molecular Characterization Project (HTMCP).

Both BLGSP and HTMCP share the similar goal of genetically characterizing a large number of tumors to delineate between different tumor subtypes. BLGSP was initiated in 2010 by the National Cancer Institute (NCI) in collaboration with the Foundation for Burkitt Lymphoma Research. Burkitt Lymphoma (BL) is a blood cancer that arises from white blood cells called B-cell lymphocytes and affects mostly children and young adults from equatorial Africa. OCG and NCI’s Office of HIV and AIDS Malignancy created HTMCP to compare genetic changes in tumors of the same organ from HIV+ and HIV- patients. HTMCP researchers are studying the most common malignancies associated with HIV infection: diffuse large B-cell lymphoma (DLBCL), cervical cancer, and lung cancer. BLGSP and HTMCP will generate a central data repository that will be accessible to the research community and include molecular characterization data from tumors and normal tissue and clinical data. For all data shared through the repository, patient privacy and confidentiality will be protected. The tumors studied in these projects afflict patients in countries around the world, and are particularly prevalent in African countries. Therefore, the findings may inform specific clinical treatments for patients across the globe.

When I entered my role as program manager, I quickly learned that standardizing protocols for tissue accrual and processing is critical for generating the quality of data necessary to establish successful data repositories for large-scale genome projects. For molecular data to be effectively analyzed, every tumor sample must be treated in a similar manner. This standardization is achieved by having technical requirements for each step of the process, which starts when patients agree to participate in the study and continues through the time when tumor samples are acquired and subsequently sent for sequencing. For example, accurate clinical data and patient consent information must be associated with each sample. Also, before samples are sent for sequencing, rigorous pathology tests are performed to confirm tumor tissues are qualified to enter the project. To read additional details about the steps involved in the tissue collection and annotation processes, visit e-News Issue 12.

To ensure that each tumor sample in the study is treated similarly, I work closely with a biospecimen core resource (BCR). The Research Institute at Nationwide Children’s Hospital (NCH) represents one BCR that performs standardized tasks, such as clinical data tracking and pathology review, for both BLGSP and HTMCP. I had the great opportunity to observe these processes first-hand when I visited NCH and interacted with a team headed by Dr. Julia Gastier-Foster. While visiting NCH, Dr. Gastier-Foster’s team provided a tour of their facilities and taught me about NCH’s tissue collection and processing procedures. This opportunity proved to be an invaluable experience for understanding the steps and attention-to-detail needed for these projects to function properly.

While organization and communication skills were necessary for my previous career as a research scientist, these skills are even more essential for my current job because of the highly collaborative nature of the projects I manage. Daily, I communicate with project team members from many institutes around the US and the world to track the progress of samples and convey the importance of carefully following protocols. To help with this, I organized the details surrounding tumor accruement and processing into easily digestible formats to better coordinate activities among the dozens of institutes and investigators involved in HTMCP and BLGSP. I designed project-specific flowcharts outlining the critical procedural steps that each project entails, re-organized tracking spreadsheets, and updated Standard Operating Procedures (SOPs), which outline detailed protocols for accruing and processing tumor samples. By carefully tracking the steps involved in tissue accrual and processing, and making sure other team members are also monitoring these steps and following SOP guidelines, we eliminate variables that may cause confounding results later in the process when molecular data are compared. These efforts will increase the likelihood that scientific discoveries, and potential new treatment options for patients, can be derived from the collected sequencing and molecular data.  

One exciting aspect of BLGSP and HTMCP is their potential to have an impact on patients around the globe. For both projects, I am coordinating with clinical sites throughout the world to acquire tumor and normal tissues for analyses. Many of these sites are in third world countries because of the abundance of BL and HIV-related tumor cases in under-developed areas. The global aspect of these projects presents various challenges, which are mostly related to the lack of resources at these sites. Most hospitals and clinical sites in third world countries do not have the tools or personnel to collect tissues according to the projects’ SOPs. Proper training and tremendous efforts from many individuals are required for these clinical sites to function properly. Fortunately, BLGSP and HTMCP have provided this training and infrastructure with the help of investigators in the United States and many on-site project team members. In fact, two on-site members at the Uganda Cancer Institute, Sarah Gerdts and Constance Namirembe, are interviewed in this e-News issue. The outcome from these efforts will help improve the timing and accuracy of cancer diagnosis and provide data that can be used to develop clinical tools to address specific disease variants present in these countries.

Now is an exciting time to be involved in these large-scale sequencing projects because of the vast amount of data produced from these studies. Information from these studies will allow us to identify somatic changes that help distinguish between different cancer subtypes of BL as well as different characteristics of tumors in HIV+ versus HIV- patients. Hopefully, in the long term, these discoveries will reveal genetic targets that can ultimately be used for improved patient treatment.