Clinical Proteomic Tumor Analysis Consortium (CPTAC) Proteogenomic Confirmatory Study of Breast, Colon, Lung, and Ovarian Tumors

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: https://cptac-data-portal.georgetown.edu/cptacPublic/

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.

• Study Weblinks:
  • Proteogenomic
• Study Design:
  • Case Set
• Study Type:
  • Case Set
  • Longitudinal
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 334
• Subject Sample Telemetry Report (SSTR)

Ovarian cohort exclusion criteria:

• Prior history of other malignancies within the past 12 months except non-melanomatous skin cancer and in situ cervical cancer.
• Other malignancies at the time of surgery.
• Any prior systemic chemotherapy or biological therapy for any cancer.
• Prior hormonal therapy within the last five years for any cancer.
• Prior radiation therapy for any prior malignancy that involves treatment to the abdomen or pelvis.
• Patients who are found to have low-grade (grade 1) or low stage (stage I or II) serous ovarian, fallopian tube, or peritoneal cancer based on final pathology (typically 5-10 days after surgery).

Colon cancer cohort exclusion criteria:

• Prior history of other malignancies within the past 12 months except basal cell carcinoma of the skin.
• Other malignancies at the time of surgery.
• Any prior systemic chemotherapy, endocrine therapy or biological therapy for any cancer.
• Prior radiation therapy to the abdomen or pelvis for any cancer, including the current cancer.

Breast cancer cohort exclusion criteria:

• Prior history of other malignancies within the past 12 months other than treated basal cell carcinoma of the skin or surgery-only treated DCIS of the ipsilateral or contralateral breast (as long as no tamoxifen was administered).
• Other malignancies at the time of surgery.
• Any prior systemic chemotherapy, endocrine therapy or biological therapy for any cancer.
• Prior history of radiation therapy involving the breast such as mantle field radiation for Hodgkins Disease, radiotherapy for lung cancer, etc.
• Patients who are found to have a diagnosis other than invasive breast cancer as a result of the surgery.

Lung cancer cohort exclusion criteria:

• Mixed histological types including adenosquamous carcinoma or adenocarcinoma with a BAC component.
• Prior history of other malignancies within the past 12 months except basal cell carcinoma of the skin.
• Other malignancies at the time of surgery.
• Any prior systemic chemotherapy, endocrine therapy or biological therapy for any cancer.
• Prior radiation therapy to the lung or thorax for any cancer, including the current cancer.

• Primary Phenotype: Neoplasms
• Ovarian Neoplasms
• Colonic Neoplasms
• Breast Neoplasms
• Carcinoma, Ductal, Breast
• Carcinoma, Lobular
• Lung Neoplasms
• Adenocarcinoma of Lung

• BioProject
• Sequence Read Archive
• BioSample
• MeSH

• Principal Investigator
  • Christopher R. Kinsinger, PhD. National Institutes of Health, Bethesda, MD, USA.
• Funding Source
  • U24CA160034. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • U24CA160019. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • U24CA160035. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • U24CA159988. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • U24CA160036. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • HHSN261201100106C. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X290. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 13XS116. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 13XS176. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 13XS179. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 13XS182. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 13XS183. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X096. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X111. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X130. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X150. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X156. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X161. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X171. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X176. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X177. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X178. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X181. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X182. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X200. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X203. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X213. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X214. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X215. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X219. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X222. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.
  • 14X225. National Institutes of Health, Bethesda, MD, USA and Leidos Biomedical Research Corporation, Frederick, MD, USA.