# Genetic and Epigenetic Biomarkers for B-cell Lymphoma

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $333,884

## Abstract

Project Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma in the United
States. Half of all DLBCLs cannot be cured with the standard immuno-chemotherapeutic regimen of rituximab,
cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Currently, the most common tool for
determining DLBLC prognosis is the International Prognostic Index (IPI), which is based on five clinical
characteristics (patient age, tumor stage, serum lactate dehydrogenase concentration, performance status,
and number of extranodal disease sites). Yet DLBCL patients with identical IPI scores exhibit marked variability
in survival, suggesting the presence of significant residual heterogeneity within each IPI category. The TP53
gene encodes the p53 tumor suppressor, the guardian of the human genome. p53 does not function properly
in most human tumors, yet it is inactivated as a direct result of mutations of the TP53 gene in only about 50%
of human tumors. Dysregulation of the p53 pathway is important to the pathogenesis of lymphoid
malignancies, including DLBCL, though mutations in the TP53 coding sequence occur in about 20% of DLBCL
patients. Through our work with the International DLBCL R-CHOP Consortium, which consists of 25 medical
centers, we obtained information leading to the hypothesis we propose to test here: genetic and non-genetic
biomarkers from the TP53 gene alone or in combination with other abnormalities can predict clinical behavior.
In this application, we propose three aims to study the potential of these suspected biomarkers. In Aim #1, we
will determine whether the combination of the IPI and immunohistochemical biomarkers, including p53, is a
more clinically accurate model than the IPI alone for predicting DLBCL prognosis. In Aim #2, we will determine
whether the combination of single-nucleotide variants in the TP53 3' untranslated region and mutations in the
TP53 coding sequence is a biomarker for DLBCL prognosis. In Aim #3, we will determine whether circulating
miRNAs and cell-free DNA are biomarkers for prognosis and relapse detection for DLBCL. Achieving the aims
in this proposal will unravel novel noncoding biomarkers in DLBCL and thereby open a new and unexplored
area of investigation for prognosis, treatment decision making, and possibly drug development for a wide range
of cancers.

## Key facts

- **NIH application ID:** 9971490
- **Project number:** 5R01CA233490-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** KEN H. YOUNG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $333,884
- **Award type:** 5
- **Project period:** 2020-01-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971490

## Citation

> US National Institutes of Health, RePORTER application 9971490, Genetic and Epigenetic Biomarkers for B-cell Lymphoma (5R01CA233490-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9971490. Licensed CC0.

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