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TCGA Completes Comprehensive Genomic Analysis of 33 Cancer Types

Jaime Rosenberg
After a decade of analyzing over 11,000 tumors from 33 types of cancer, the collaboration between the National Cancer Institute and National Human Genome Research Institute has launched the Pan-Cancer Atlas, providing a comprehensive understanding of 3 focus areas: cell-of-origin patterns, oncogenic processes, and signaling pathways.
Over the past decade, researchers from The Cancer Genome Atlas (TCGA), a collaboration led by the National Institutes of Health and the National Human Genome Research Institute, have worked to identify and develop a comprehensive understanding of genomic changes in cancer. After analyzing more than 11,000 tumors from 33 types of cancers, TCGA has launched the Pan-Cancer Atlas.

“The Pan-Cancer Atlas provides a uniquely comprehensive, in-depth, and interconnected understanding of how, where, and why tumors arise in humans,” states the Atlas. “As a singular and unified point of reference, the Pan-Cancer Atlas is an essential resource for the development of new treatments in the pursuit of precision medicine.”

The Pan-Cancer Atlas includes 27 studies divided into 3 designated categories: cell-of-origin patterns, oncogenic processes, and signaling pathways. Each category has a flagship paper, accompanied by companion papers giving a deeper dive into subtopics of the category.

The first flagship paper summarizes findings from the molecular classification of 10,000 tumors from 33 types of cancer. The classification grouped tumors by different identifiers, such as abnormality of chromosome numbers in tumor cells and DNA modifications, and found that tumor types cluster by their possible cells of origin. The authors concluded that cell-of-origin influences, but does not fully determine, tumor classification.

“Tumor location has been the primary method for determining treatment for a given cancer patient,” said Katherine Hoadley, PhD, assistant professor at the University of North Carolina’s (UNC) School of Medicine and the paper’s first co-corresponding author, in a UNC press release. “This study helps us get a better understanding of the relationship across and within different tumor types. If tumors are genetically diverse within an organ, we should rethink the way we treat them.”

In the second flagship paper, researches provide an overview of the processes leading to cancer development and progression through analyses on oncogenic molecular processes. Researchers noted 3 processes: somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; the influence of the tumor genome and epigenome on transcriptome and proteome; and the relationship between the tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies.

“These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinic genomic sequencing,” wrote the researchers.

Findings from investigations on genomic alterations in signaling pathways that control cell cycle progression, cell death, and cell growth were presented in the third flagship paper. The investigations highlighted the similarities and differences between these processes amongst a range of cancers. Results revealed that 89% of tumors had at least 1 driver alteration in these pathways, 57% of tumors had at least 1 alteration potentially targetable by a currently available therapy, and 30% of tumors has multiple targetable alterations.

Precision medicine is increasingly being utilized in oncology, with the Pan-Cancer Atlas representing the most recent stride. In January, Syapse and Roche joined forces to and develop software products and analytics solutions that empower healthcare providers with the tools and insights needed to practice precision medicine at scale.

In December last year, the FDA-approved FoundationOne CDx, the first-of-a-kind comprehensive companion diagnostic test for solid tumors. By looking at the 324 genes known to drive cancer growth, the test gives patients the ability to accurately be matched with an available targeted therapy or be matched to a clinical trial and can potentially open the door to the development of new targeted therapies.

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