This project is a continuation of Project 1 A. Significant progress was made on each of the original aims of this project. Our goals related to improved presymptomatic diagnosis of individuals with inherited predispositions to cancer were essentially obtained and that aim has been retired. Our work related to early detection continued to show that somatic mutations can be sensitive and specific markers of neoplastic cells. Moreover, the development of a new technology called BEAMing, which allows hundred of thousands of individual PCRs to be performed in one tube, further improved our ability to detect somatic mutations. In total, our studies suggest that somatic mutations have the potential to significantly outperform conventional markers for early detection. Accordingly, our current proposal will focus on three aims related to the application of somatic mutations for the early detection of neoplasia.
Aim #1 will focus on identification of somatic mutations in fecal DMAfor the early detection of colorectal cancers and adenomas. Specifically, we will develop and validate a Stool Mutation Test (SMT) capable of detecting clinically relevant adenomas and cancers with >70% and >90% sensitivity, respectively, and >99% specificity.
Aim #2 will focus on identification of somatic mutations in plasma DMAfor the detection of colorectal cancers. The major goal of this aim is development and validation of a Plasma Mutation Test (PMT) capable of detecting early colorectal cancers (Dukes A and B) with >50% sensitivity and >99% specificity.
Aim #3 will focus on identification of somatic mutations in plasma DMA for the early detection of pancreatic cancers. The goal of this aim is to develop and validate a PMT capable of detecting early pancreatic cancers (Stage I and II) with >50% sensitivity and >99% specificity. These studies will utilize samples from Cores 2 and 3 to translate discoveries made in former Projects 1A and 1B to patient care. We will provide tools for early screening of patients in Core 3 familial registries, help in the characterization of patients evaluated in Project 3A and aid development of new approaches by Projects 2B and 3B. The overall goal of the above studies is to provide clinically practical assays for early detection and management of colorectal and pancreatic cancers. From a public health prospective, such early detection strategies have the best chance of reducing the morbidity and mortality associated with colorectal and pancreatic cancers in the near term.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA062924-17
Application #
8096764
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
17
Fiscal Year
2010
Total Cost
$295,134
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Christmas, Brian J; Rafie, Christine I; Hopkins, Alexander C et al. (2018) Entinostat Converts Immune-Resistant Breast and Pancreatic Cancers into Checkpoint-Responsive Tumors by Reprogramming Tumor-Infiltrating MDSCs. Cancer Immunol Res 6:1561-1577
Blair, Alex B; Murphy, Adrian (2018) Immunotherapy as a treatment for biliary tract cancers: A review of approaches with an eye to the future. Curr Probl Cancer 42:49-58
Raman, Aadhithya; Lennon, Anne Marie (2018) Cyst Fluid Biomarkers - Diagnosis and Prediction of Malignancy for Cystic Lesions of the Pancreas. Visc Med 34:178-181
Noë, Michaël; Pea, Antonio; Luchini, Claudio et al. (2018) Whole-exome sequencing of duodenal neuroendocrine tumors in patients with neurofibromatosis type 1. Mod Pathol 31:1532-1538
Cohen, Joshua D; Li, Lu; Wang, Yuxuan et al. (2018) Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 359:926-930
Shumar, Stephanie A; Kerr, Evan W; Geldenhuys, Werner J et al. (2018) Nudt19 is a renal CoA diphosphohydrolase with biochemical and regulatory properties that are distinct from the hepatic Nudt7 isoform. J Biol Chem 293:4134-4148
Li, Yuguo; Qiao, Yuan; Chen, Hanwei et al. (2018) Characterization of tumor vascular permeability using natural dextrans and CEST MRI. Magn Reson Med 79:1001-1009
Saung, May Tun; Muth, Stephen; Ding, Ding et al. (2018) Targeting myeloid-inflamed tumor with anti-CSF-1R antibody expands CD137+ effector T-cells in the murine model of pancreatic cancer. J Immunother Cancer 6:118
Canto, Marcia Irene; Almario, Jose Alejandro; Schulick, Richard D et al. (2018) Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance. Gastroenterology 155:740-751.e2
Makohon-Moore, Alvin P; Matsukuma, Karen; Zhang, Ming et al. (2018) Precancerous neoplastic cells can move through the pancreatic ductal system. Nature 561:201-205

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