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Discovering the causes of cancer and the means of prevention

Celebrating 15 Years of the Cancer Genomics Research Laboratory

, by DCEG Staff

A fleet of desktop sequencers in the CGR.

October 2016 marks the 15th anniversary of the founding of the DCEG Cancer Genomics Research (CGR) Laboratory. From the outset, CGR has responded to new scientific opportunities by incorporating the latest technologies, enabling DCEG investigators to be at the cutting edge of discovery. Initially, projects focused on candidate single-nucleotide polymorphisms (SNPs), which relied on educated guesses to search for base pair variations drawn from particular genes that could be associated with cancer. The process was slow and ineffective. The development of massively parallel genotyping of SNPs on microarray chips revolutionized the scientific approach, enabling investigators to agnostically scan across the genome in search of markers that point to a region involved in cancer risk. This required larger scale studies and new biostatistical analysis techniques. CGR has also capitalized on advances in sequencing technologies that similarly can survey variation across target genes, the protein coding regions known as the exome, and more recently the entire genome. These new studies have required expertise in analyses of the germline DNA and have been extended to the somatic alterations characteristic of cancer genomes. Studies are also utilizing whole-genome methylation and RNA sequencing technologies to more fully elucidate the functional impact of genetic variation in cancer.

CGR leadership has developed a solid scientific foundation to conduct of a wide range of studies that includes expertise in sample handling, quality control metrics, bioinformatics and sophisticated genetic analyses. They have implemented and updated an elaborate information management system to handle the enormous amount of data generated, which already exceeds 4.5 petabytes.

“If someone had told me fifteen years ago that we’d be accomplishing as much as we are today, I wouldn’t have believed them,” said Meredith Yeager, Ph.D., scientific director of CGR. “The lab remains central to the international effort to understand how our DNA can affect our risk of cancer.”

CGR directors from left to right: Joseph Boland, Meredith Yeager, Amy Hutchinson, and Belynda Hicks.

At its founding in 2001, CGR, then known as the Core Genotyping Facility, was directed by Stephen Chanock, M.D., Director, DCEG and CGR, alongside a scientific and operations management team that included Dr. Yeager, the late Robert Welch, M.B.A., deputy director, and Amy Hutchinson, M.S., director of operations. Belynda Hicks, M.S., deputy director, and Joseph Boland, M.B.A., director of research and development have since joined the lab. They are supported by an outstanding team of technicians, information and data management scientists, administrative support and quality control and project management staff.

Recently, CGR has turned its genetic expertise towards the analysis of the human papillomaviruses (HPV), which are known to cause cancer, particularly cervical cancer, but also at other sites in the body. They have shown that different types of the virus, and specific isolates within those types, have varying degrees of carcinogenicity. Studies of viral DNA sequences now point to which ones are most likely to lead to pre-cancer and cancer.

CGR continues to push the boundaries with both technological and analytical capabilities. Leveraging new sequencing applications from Oxford Nanopore, 10X Genomics and Pacific Biosciences allows CGR and DCEG to more fully assess structural variation, gene fusions and haplotype analysis. New efforts in microbiome research are poised to elucidate the connection between cancer and microbial diversity. Molecular and digital pathology capabilities are planned to be added over the next year, and will allow our investigators to leverage the rich specimen resources available within the Division. CGR and DCEG promise to continue to identify and apply the newest and most advanced laboratory and bioinformatics tools to explore germline and somatic contributions to cancer.

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