METHYLATION BIOMARKER DEVELOPMENT FOR NONINVASIVE DETECTION OF COLORECTAL CANCER

Information

  • Research Project
  • 9477478
  • ApplicationId
    9477478
  • Core Project Number
    R01CA181572
  • Full Project Number
    5R01CA181572-05
  • Serial Number
    181572
  • FOA Number
    PA-11-260
  • Sub Project Id
  • Project Start Date
    5/21/2014 - 10 years ago
  • Project End Date
    4/30/2019 - 5 years ago
  • Program Officer Name
    YOUNG, MATTHEW R
  • Budget Start Date
    5/1/2018 - 6 years ago
  • Budget End Date
    4/30/2019 - 5 years ago
  • Fiscal Year
    2018
  • Support Year
    05
  • Suffix
  • Award Notice Date
    4/27/2018 - 6 years ago

METHYLATION BIOMARKER DEVELOPMENT FOR NONINVASIVE DETECTION OF COLORECTAL CANCER

DESCRIPTION (provided by applicant): Colorectal carcinoma (CRC) is the third most common cancer in the United States, with an estimated 150,000 new cases occurring annually. Early detection of clinically relevant colorectal neoplasia (CRN), i.e., CRC and advanced colorectal adenomas (A-CRA), is the best way to improve survival. However, available screening modalities are impractical due to invasiveness and cost (i.e., colonoscopy) or insufficient diagnostic accuracy (i.e., fecal-based blood tests). A better approach to screening and surveillance would be highly desirable. Abnormal DNA methylation is an important epigenetic mechanism that has been strongly implicated in the pathogenesis and progression of colorectal neoplasia. Aberrant DNA methylation is detectable in serum making it an ideal candidate biomarker species for non-invasive screening. Previous studies have achieved limited success in developing definitive sets of methylation biomarkers for CRC screening due non-comprehensive approaches, and a failure to include all CRNs as meaningful targets for clinical discovery. Also, cohorts used in serum-based studies have been insufficiently powered and lacked independent validation sets. In this proposal, innovative strategies will be applied to permit genome-scale methylation mapping using tissues and sera from patients with CRN, and compared with tissues and sera from individuals without CRN. A novel and powerful new approach is being proposed to identify new biomarkers and methylation targets with the highest sensitivity and specificity, and will be validated using large, well- characterized sample sets through the following Specific Aims. Aim 1: Candidate DNA methylation biomarkers will be discovered using next generation bisulfite sequencing in matched tissue and serum from patients with CRN and individuals with a normal colon. Aim 2: Candidate serum methylation biomarkers will be discovered that distinguish patients with CRN vs. those without CRN, and validated biomarkers using quantitative PCR assays. Aim 3: Clinical validation of prioritized serum methylation biomarkers identified in Aim 2b will be performed in asymptomatic average risk individuals. The innovation of this project is based upon the first use of a novel, next generation sequencing-based approach for identifying methylation-based biomarkers using a genome-scale assay for methylation sites linked to colorectal neoplasia, and validating these newly discovered biomarkers using a large, well-characterized cohort of patients with CRN and controls. The long-term goal and potential impact of this project is to develop a sensitive, specific, non-invasive and inexpensive diagnostic test for early colorectal neoplasia.

IC Name
NATIONAL CANCER INSTITUTE
  • Activity
    R01
  • Administering IC
    CA
  • Application Type
    5
  • Direct Cost Amount
    208422
  • Indirect Cost Amount
    111313
  • Total Cost
    319735
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    394
  • Ed Inst. Type
  • Funding ICs
    NCI:319735\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    BAYLOR RESEARCH INSTITUTE
  • Organization Department
  • Organization DUNS
    145745022
  • Organization City
    DALLAS
  • Organization State
    TX
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    752046165
  • Organization District
    UNITED STATES