Project description:Recently, significant progress has been made in characterizing and sequencing the genomic alterations in statistically robust numbers of samples from several types of cancer. For example, The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and other similar efforts are identifying genomic alterations associated with specific cancers (e.g., copy number aberrations, rearrangements, point mutations, epigenomic changes, etc.). The availability of these multi-dimensional data to the scientific community sets the stage for the development of new molecularly targeted cancer interventions. Understanding the comprehensive functional changes in cancer proteomes arising from genomic alterations and other factors is the next logical step in the development of high-value candidate protein biomarkers. Hence, proteomics can greatly advance the understanding of molecular mechanisms of disease pathology via the analysis of changes in protein expression, their modifications and variations, as well as protein-protein interaction, signaling pathways and networks responsible for cellular functions such as apoptosis and oncogenesis. Realizing this great potential, the NCI launched the second phase of the CPTC initiative in September 2011. Renamed the Clinical Proteomic Tumor Analysis Consortium, CPTAC is beginning to leverage its analytical outputs from Phase I to define cancer proteomes on genomically-characterized biospecimens. The purpose of this integrative approach is to provide the broad scientific community with knowledge that links genotype to proteotype and ultimately phenotype. The data contained in this dataset are derived from samples designed to confirm CPTAC findings from the TCGA samples. These confirmatory samples contain breast, ovarian, colon, and lung tumors collected via a protocol optimized for proteomics. Specifically, ischemic time of the sample was controlled and restricted to less than 30 minutes. ACGT, Inc. produced whole exome, mRNAseq, and miRNAseq for these samples. Corresponding proteomic data are available at: <a href="https://cptac-data-portal.georgetown.edu/cptacPublic/">https://cptac-data-portal.georgetown.edu/cptacPublic/</a> The study design was to profile colon, breast, ovarian, and lung tumors both genomically and proteomically. Germline DNA was obtained from blood. Normal control samples for proteomics varied by organ site: adjacent colon tissue for colon cases, contralateral breast tissue for some breast cases, and Fallopian tube fimbria for some ovarian cases. Lung cases had no normal control for proteomic analysis. All cancer samples were derived from primary and untreated tumors.

Project description:Tissue for this CPTAC study was collected and characterized for a confirmatory cohort of 125 individuals with breast cancer. Quantitative mass-spectrometry-based proteomic, phosphoproteomic, and acetylome analyses were performed on breast tumors (125 participants) and adjacent normal breast tissue (18 participants). The analyses of this CPTAC cohort were conducted in order to more extensively characterize the proteogenomic landscape of breast cancer initially described in the publication by <a href="https://www.ncbi.nlm.nih.gov/pubmed/27251275" target="_blank">Mertins et al., (Nature 2016)</a>. Data were generated with TMT10plex quantification and each 10-plex experiment contained a common reference sample composed of a pooled mixture of 40 tumor samples. There are 17 global proteomic 10-plex datasets each with 25 fractions, 17 phosphoproteomic 10-plex datasets each with 13 fractions, and 17 acetylome 10-plex datasets each with 6 fractions. Raw LC-MS/MS (level 1 data) provided below are from investigators at the Proteome Characterization Center located at the Broad Institute of MIT and Harvard. Raw data were processed through the CPTAC Common Data Analysis Pipeline (CDAP) to produce peptide spectrum match reports (level 2 data) and protein summary reports (level 3 data), which are also provided below.TMT phosphoproteome data were generated twice for plex #2 ,02CPTAC_BCProspective_Phosphoproteome_BI. The first replicate (20160928) had an uncharacteristically low phosphopeptide enrichment rate of 72%, typical values are > 90%. Hence, the IMAC flow thru was re-enriched to generate a second dataset (20170303). However, the second replicate yielded only 60% as many phosphopeptides and the phospho-enrichment rate was worse, 62%. Consequently, only the "20160928" dataset will be used in the final analyses, the second dataset (20170303) is labeled "deprecated." ' <ul><li>Dataset imported into MassIVE from <a href="https://cptac-data-portal.georgetown.edu/study-summary/S039">https://cptac-data-portal.georgetown.edu/study-summary/S039</a> on 01/25/21</li></ul>

Project description:<a href="https://cptac-data-portal.georgetown.edu/study-summary/S056" target="_blank">Proteogenomics of Lung Adenocarcinoma, Gillette et al., 2020 publication is here</a> Lung cancer is a leading cause of cancer death in the United States and in 2019 it is estimated that there will be over 228,000 new cases (<a href="https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html" target="_blank">American Cancer Society</a>). There are two main types, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). A majority of patients (85%) have NSCLC, with a significant portion of those individuals having a histological subtype lung adenocarcinoma (LUAD) <a href="https://www.ncbi.nlm.nih.gov/pubmed/29364287" target="_blank">Herbst et al., 2018 Nature</a>. To advance the proteogenomic understanding of LUAD, the CPTAC program has investigated 111 tumors, (with 102 tumors paired with normal adjacent tissue samples) and subjected these samples to global proteome and phosphoproteome analysis. An optimized workflow for mass spectrometry of tissues using isobaric tags (TMT (tandem mass tags)-10) was used (<a href="https://www.ncbi.nlm.nih.gov/pubmed/29988108" target="_blank">Mertins et al., Nature Protocols 2018</a>). Proteome and phosphoproteome data from the LUAD discovery cohort is available below along with peptide spectrum matches (PSMs) and protein summary reports from the CPTAC common data analysis pipeline (CDAP).Clinical Data for LUAD tumors are provided below. Updates will be available as the LUAD cohort characterization proceeds. Genomic Data for LUAD tumors is available from the NCI Genomic Data Commons (GDC), <a href="https://portal.gdc.cancer.gov/projects/CPTAC-3" target="_blank">here</a> Imaging Data for LUAD tumors is available from NCI, The Cancer Imaging Archive (TCIA), <a href="https://wiki.cancerimagingarchive.net/display/Public/CPTAC-LUAD" target="_blank">here</a> This release includes over 4500 files and 914 GB of data. <ul><li>Dataset imported into MassIVE from <a href="https://cptac-data-portal.georgetown.edu/study-summary/S046">https://cptac-data-portal.georgetown.edu/study-summary/S046</a> on 01/29/21</li></ul>

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CPTAC Proteogenomic Confirmatory Study

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