# Genomic biomarkers for cutaneous T-cell Lymphoma

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $650,784

## Abstract

PROJECT SUMMARY
Peripheral T-cell lymphomas including cutaneous T-cell lymphomas (CTCL) are poorly understood and many
subtypes exhibit aggressive clinical course and high mortality with short (2-year) life expectancy after
diagnosis. Poor understanding of mechanisms underlying the pathogenesis of CTCLs contributes to
suboptimal diagnostic subcategorization and lack of targeted therapies. Mycosis fungoides (MF) and Sezary
syndrome (SS) are two major forms of CTCL. Clinical staging and outcome of MF and SS is dependent on
the quantity of neoplastic cells in the blood. While SS is an aggressive disease with poor overall survival
(42.3% at 5 years and is by definition diagnosed at late stage disease, there are many patients with low
tumor burden (Early-stage CTCL) who suffer from delay in diagnosis due to the subjective nature of the
diagnostic criteria. The mean diagnostic delay (measured as the time from emergence of skin lesions to the
diagnosis of SS) is long (4.2 year; median 2.8 years) with a significant variation (1 month to 32 years).
Thus, there is a critical need for improved methods for early disease detection. Furthermore, the
identification of genomic disease biomarkers that would establish early diagnosis and provide prognostic
information would clearly have benefit for patients with this form of aggressive CTCL. Until recently,
recurrent genetic alterations that can be exploited as diagnostic and prognostic biomarkers have not been
described in these tumors. Our laboratory and other investigators recently described the genomic
landscape of CTCL utilizing a comprehensive integrated strategy including whole genome sequencing,
whole exome sequencing and array comparative gnomic hybridization. Highly recurrent gene mutations
targeting epigenetic and chromatin remodeling and JAK-STAT and other pathways were identified in pre-
treatment samples of CTCL. Based on these results, it is our central hypothesis that somatic alterations
involved in the pathogenesis of CTCL in conjunction with high-throughput sequencing (HTS) of the T-cell
receptor (TCR) can be utilized for early diagnosis and that genetic profiles and sensitive and
quantitative detection of clonal T-cell populations can serve as prognostically-relevant biomarkers of
CTCL. Accordingly, in Specific Aim 1, we propose to investigate the utility of a multivariate model based on
targeted next generation sequencing (NGS) and HTS-TCR assays for the diagnosis of ES-CTCL and Late-
stage CTCL (SS). In Specific Aim 2, we will investigate the impact of the genetic mutations and HTS-TCR
on the prognosis of ES-CTCL and SS using a retrospective cohort. In Specific Aim 3, we will assess
the performance of the multivariate model for assessing the prognosis of ES-CTCL and SS using a
prospective cohort. The overall impact of this proposal is the development of targeted genomic assays that
will lead to early and accurate diagnosis of CTCL and improve methods to assess early disease detection
and progn...

## Key facts

- **NIH application ID:** 10107797
- **Project number:** 5R01CA238552-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Megan S. Lim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $650,784
- **Award type:** 5
- **Project period:** 2020-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10107797

## Citation

> US National Institutes of Health, RePORTER application 10107797, Genomic biomarkers for cutaneous T-cell Lymphoma (5R01CA238552-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10107797. Licensed CC0.

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