Proteogenomic Study of Breast Cancer May Yield New Target

If it takes a village to raise a child, it is taking multiple villages to find the best theraputic targets for breast cancer. As a collaborative effort of several cancer centers throughout the United States, teams of researchers have completed the first large-scale proteogenomic study of breast cancer-effectively linking DNA mutations to protein signaling to pinpoint the genes that drive cancer growth.

Scientists from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), including Baylor College of Medicine, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Fred Hutchinson Cancer Research Center, New York University Langone Medical Center, and Washington University School of Medicine, have built on the data provided by the The Cancer Genome Atlas (TCGA) project, to study proteins and their role in cancer growth. They studied 77 breast cancer tumors that had been genomically characterized in the TCGA project. This study was first reported in the journal Nature online May 25, 2016.

Using high-resolution mass spectrometry, the analysis revealed new protein markers and signaling pathways for breast cancer subtypes and tumors carrying frequent mutations such as PIK3CA and TP53. Researchers correlated copy number alterations in some genes with protein levels, allowing them to identify 10 new candidate regulators including SKP1 and CETN3, which is associated with EGFR.

It is interesting to note that not all mutated genes activate cancer growth, some have little function. However, others are found within very large DNA regions that are deleted or appear to have extra copies, so separating the specific genes by studying the activity of their protein products can help identify other potential therapeutic targets beyond HER2.

“We don’t fully understand how complex cancer genomes translate into the driving biology that causes relapse and mortality,” said Matthew Ellis, BSc. MB, BChir, PhD, FRCP, professor and director of the Lester and Sue Smith Breast Center at Baylor College of Medicine, in a news release. “These findings show that proteogenomic integration could one day prove to be a powerful clinical tool, allowing us to traverse the large knowledge gap between cancer genomics and clinical action.”

One of the challenges in studying breast cancer tumors is the number of variables. They contain many mutations-consequently, the team studies the cancer cells that have mutations which have evolved in order to analyze the cell's proteins rather than to cast a wide net and conduct endless studies.