The incidence of neuroendocrine tumors is increasing, and the annual prevalence of these malignancies is estimated to exceed 100,000 individuals in the United States. Neuroendocrine tumors are rarely associated with inherited genetic syndromes;however, risk factors for the vast majority of """"""""sporadic"""""""" neuroendocrine tumors have not been identified. Similarly, prognostic factors for these tumors are poorly understood. The identification of genetic and molecular prognostic factors for neuroendocrine tumors was identified as a key research priority at a National Cancer Institute summit meeting in September, 2007. Our proposed studies will leverage the resources of a large database of neuroendocrine tumor patients and biospecimens, developed by the PI during his prior K23 career development award. The database provides detailed clinical, pathologic, and outcome data, together with banked germline DNA and archived tumor specimens.
Our aims are informed by recent preclinical and clinical data suggesting key roles for angiogenesis and mTOR signaling, as well as by a previous analysis of genomic aberrations in neuroendocrine tumors, performed by the PI.
In Aim 1, we propose a two-stage candidate SNP approach to identify and then confirm genetic predictors of risk or survival in these pathways.
In Aim 2, we propose to identify and validate immunohistochemical predictors of survival for in these same pathways.
In Aim 3, we will assess the potential prognostic significance of chromosome 14q11 amplification or chromosome 18 LOH in small bowel carcinoid tumors. The results will inform our understanding of neuroendocrine tumor risk, prognosis, and biology. Our studies will also potentially identify at-risk populations and new therapeutic targets for this disease. Beyond the proposed aims, this database and specimen repository will allow for the rapid examination of future hypotheses as they emerge.

Public Health Relevance

The diagnosed incidence of neuroendocrine tumors is increasing, yet the genetic and molecular underpinnings of this disease are poorly understood. Our project focuses on identifying genetic and molecular predictors of neuroendocrine tumor risk and prognosis. The results will help identify patients at risk for this disease, identify clinically useful prognostic markers, and identify novel therapeutic targets.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA151532-02
Application #
8328884
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Sorg, Brian S
Project Start
2011-09-06
Project End
2015-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$629,307
Indirect Cost
$152,514
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
da Silva, Annacarolina; Bowden, Michaela; Zhang, Sui et al. (2018) Characterization of the Neuroendocrine Tumor Immune Microenvironment. Pancreas 47:1123-1129
Shi, Yan; Qian, Zhi Rong; Zhang, Sui et al. (2017) Cell Cycle Protein Expression in Neuroendocrine Tumors: Association of CDK4/CDK6, CCND1, and Phosphorylated Retinoblastoma Protein With Proliferative Index. Pancreas 46:1347-1353
Bowden, Michaela; Zhou, Chensheng W; Zhang, Sui et al. (2017) Profiling of metastatic small intestine neuroendocrine tumors reveals characteristic miRNAs detectable in plasma. Oncotarget 8:54331-54344
Ter-Minassian, Monica; Zhang, Sui; Brooks, Nichole V et al. (2017) Association Between Tumor Progression Endpoints and Overall Survival in Patients with Advanced Neuroendocrine Tumors. Oncologist 22:165-172
Qian, Zhi Rong; Li, Tingting; Ter-Minassian, Monica et al. (2016) Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors. Pancreas 45:1386-1393
Du, Yeting; Ter-Minassian, Monica; Brais, Lauren et al. (2016) Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study. Endocr Relat Cancer 23:587-94
Roy, R; Zurakowski, D; Wischhusen, J et al. (2014) Urinary TIMP-1 and MMP-2 levels detect the presence of pancreatic malignancies. Br J Cancer 111:1772-9
Kulke, Matthew H (2013) Systemic therapy for advanced pancreatic neuroendocrine tumors. Semin Oncol 40:75-83
Chan, Jennifer A; Kulke, Mathew H (2013) Reply to A. Koumarianou et al and J. Hadoux et al. J Clin Oncol 31:977-8
Ter-Minassian, Monica; Chan, Jennifer A; Hooshmand, Susanne M et al. (2013) Clinical presentation, recurrence, and survival in patients with neuroendocrine tumors: results from a prospective institutional database. Endocr Relat Cancer 20:187-96

Showing the most recent 10 out of 18 publications