Chuck Perou, PhD, the May Goldman Shaw Distinguished Professor of Molecular Oncology and a member of UNC Lineberger, was a co-author of a study published in the journal Nature. Building on data from The Cancer Genome Atlas (TCGA) project, Perou and a multi-institutional team of scientists completed the first large-scale “proteogenomic” study of breast cancer, linking DNA mutations to protein signaling and helping pinpoint the genes that drive cancer.
Conducted by members of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), including Baylor College of Medicine, Broad Institute of MIT and Harvard, Fred Hutchinson Cancer Research Center, Icahn School of Medicine at Mount Sinai, New York University Langone Medical Center, and Washington University School of Medicine, the study takes aim at proteins, the workhorses of the cell, and their modifications to better understand cancer. Appearing in Nature online May 25, the study illustrates the power of integrating genomic and proteomic data to yield a more complete picture of cancer biology than either analysis could do alone.
The effort produced a broad overview of the landscape of the proteome (all the proteins found in a cell) and the phosphoproteome (the sites at which proteins are tagged by phosphorylation, a chemical modification that drives communication in the cell) across a set of 77 breast cancer tumors that had been genomically characterized in the TCGA project. Although the TCGA produced an extensive catalog of somatic mutations found in cancer, the effects of many of those mutations on cellular functions or patients’ outcomes are unknown. In addition, not all mutated genes are true “drivers” of cancer — some are merely “passenger” mutations that have little functional consequence. And some mutations are found within very large DNA regions that are deleted or present in extra copies, so winnowing the list of candidate genes by studying the activity of their protein products can help identify therapeutic targets.
“The significance of this work is the great power of the proteogenomics approach, which is the melding together of genome wide genomic techniques with genome-wide proteomic techniques,” Perou said. “Using samples coming from the TCGA Project multiple cutting edge proteomic approaches were applied to a set of breast tumors that had already had extensive analyses done in the TCGA, including RNA-sequencing and DNA-sequencing. We found many commonalities between the RNA and Protein work, and the protein analysis also revealed a number of findings including the identification of few new therapeutic targets.”