Based on data from the Cancer Genome Atlas (TCGA) program, a multi-agency team of scientists completed the first large-scale breast cancer “protein genomics” (proteogenomic) study, some of the DNA mutation and protein signals linked together, and help determine Some drivers cancer genes.
This study aims to proteins and their modifications to better understand cancer. Published in the May 25 “Nature” (Nature) magazine research papers confirmed compared to the individual using any method of analysis, integration of genomic and proteomic data to generate a more complete picture of the ability of cancer biology.
Dr. Matthew Ellis, a senior author on the paper, director of the Baylor Medical Lester and Sue Smith Breast Center and professor, said: “We do not how to fully understand the complexity of the cancer genome is converted to lead to relapse and death drive biology These findings suggest that integration. protein genomics may one day prove to be a powerful clinical tool that allows us to cross huge knowledge gap between science and clinical effects of cancer genomes. ”
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The research efforts of TCGA plan has identified Genomics features 77 breast tumor protein group and phosphoproteome (phosphoproteome) extensive information landscape. Despite TCGA generated extensive catalog of somatic mutations in cancer, it is currently unclear which affects many mutations on cell function or patient outcomes. Moreover, not all mutations are real cancer “drivers” – just some of the function of small “passenger” mutations. Some mutations were found in the deleted region of great DNA or extra copies, so by studying the activity of the protein product of their list of candidates to filter out genes can help identify therapeutic targets.
In this study, researchers analyzed breast tumors using accurate high-resolution mass spectrometry, the technology to expand the coverage of the genome than the traditional antibody-based methods. This enables them to expand research efforts to quantify more than 12,000 and 33,000 protein phosphorylation sites – a deep level of coverage.
Senior author of the paper, Dr. Steven Carr Broad Institute of Proteomics platform director, said: “The development of instruments for sample preparation and mass spectrometry-based proteomics brought about a revolution we can now apply phosphorylated protein group – – this is great for cancer and other diseases in signaling our approach is essential in order to achieve scale in the past can not generate a strong and repeatable data. “.
Like other cancers, breast cancer and has a plurality of mutations, so they require numerous experimental studies to understand the mutations in model systems of various combinations of. With this method, the team studied the evolution of cancer these mutations occur, and analyzes the overall production of cellular proteins.
For some of the breast cancer subtypes and carry common mutations such as PIK3CA and TP53 mutant tumors, analysis of the results revealed a number of new protein markers and signaling pathways. The researchers also some of the gene copy number changes (extra or missing DNA) and protein level contact together, so that they identified 10 new candidate regulatory factors. Two candidate genes SKP1 and CETN3 may be associated with cancer gene EGFR. EGFR is a particularly invasive breast cancer subtypes – “basal-like” tumor markers.
The use of transcription (mRNA) analysis, scientists will be divided into four main breast cancer subtypes: luminal A and B subtypes, basal-like tumors, and rich HER2 tumors. In this work, the researchers used proteomics and phosphoric proteomic data outlines the substrate and luminal subtypes. They also managed based on the phosphorylation of signaling pathways identified a cluster of tumor matrix-rich clusters, and to clarify the use of mRNA using methods not see a G protein-coupled receptor subgroup.
In the study and treatment of breast cancer, scientists and doctors are hoping to find more available drugs except HER2 protein kinase control. Trastuzumab (Herceptin) may be targeted HER2, but this protein exists only in 20% of breast cancer. In this study, the researchers analyzed the number of isolated points kinase phosphorylation status, highlighting some of the breast cancer samples aberrantly activated kinases such as HER2, CDK12, PAK1, PTK2, RIPK2 and TLK2.
Protein genome using proteomics data, especially high-precision tandem mass spectrometry data, combined with genomic and transcriptome data for genome annotation. Proteomic data not only on the annotated genes verification and correction, and then the discovery of new genes to achieve the re-annotation of genomic sequences, but also the system-specific protein translation was found after an event (such as signal peptide and post-translational modifications, etc.). With the rapid development of tandem mass spectrometry based proteomics, genomics, protein has become an important tool for functional genomics indispensable. In 2014, Ge peak group of Hydrobiology, Chinese Academy of Sciences in cooperation with the Tao group of models cyanobacteria Synechococcus sp. PCC 7002 genome protein school has been systematically studied, research papers published in the journal PNAS.
In 2014, by a team led by Vanderbilt University identified a number of genetic mutations drive colorectal cancer protein “tag.” This important study published in the journal Nature, the first comprehensive Analyses of human cancer “proteome – genomics” feature, which will promote colorectal (colorectal) cancer diagnosis and treatment has made new progress.
By far the largest group of breast cancer whole genome sequencing studies, reveals five new genes associated with the disease, and the impact of tumor growth 13 new mutations tags. Results published in the journal Nature Communications 2016 Nature and two research papers, but also reveals the presence of breast cancer in some genetic variation and their occurrence in the genome.