Genomic biomarkers for cutaneous T-cell Lymphoma
皮肤 T 细胞淋巴瘤的基因组生物标志物
基本信息
- 批准号:10703843
- 负责人:
- 金额:$ 17.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-10-01 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:Aggressive Clinical CourseBehaviorBioinformaticsBiological AssayBiological MarkersBiometryBloodClassificationClinicalCutaneous T-cell lymphomaDNA Sequence AlterationDetectionDevelopmentDiagnosisDiagnosticDiseaseEarly DiagnosisEnvironmentEpigenetic ProcessExhibitsGene MutationGeneticGenomicsGoalsHigh-Throughput Nucleotide SequencingIndolentLaboratoriesLearningLife ExpectancyLymphomaMeasuresMethodsModelingMutationMycosis FungoidesNatureNeoplasm Circulating CellsOncogenicOutcomePathogenesisPathway interactionsPatientsPennsylvaniaPerformancePeripheralPopulationPrognosisPrognostic MarkerProspective cohortRecurrenceResearchResearch PersonnelRetrospective cohortSamplingSezary SyndromeSkinSkin CancerStagingSubgroupT cell receptor repertoire sequencingT-Cell LymphomaT-Cell Receptor GenesT-LymphocyteTestingTimeTumor BurdenUniversitiesVariantaccurate diagnosisbasechromatin remodelingcohortcomparativecomparative genomic hybridizationdiagnostic biomarkerdiagnostic criteriadiagnostic paneldiagnostic tooldisorder riskexome sequencinggenome sequencinggenomic biomarkerimprovedindexingleukemiamortalityneoplastic cellnext generation sequencingnovelpatient subsetsprognosticprognostic significanceprognostic toolprognosticationrisk stratificationskin lesionspecific biomarkerstargeted treatmenttumorwhole genome
项目摘要
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 prognosis.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Megan S. Lim其他文献
Pilot Study Using Induction Chemo-Immunotherapy Followed By Consolidation with Reduced Toxicity Conditioning and Allogeneic Stem Cell Transplant in Advanced Stage Mature Non-Anaplastic T- or NK-Cell Lymphoma/Leukemia in Children, Adolescent, and Young Adults
- DOI:
10.1182/blood-2022-160045 - 发表时间:
2022-11-15 - 期刊:
- 影响因子:
- 作者:
Ana C. Xavier;Lauren Harrison;Rodney R. Miles;Stephan Voss;Megan S. Lim;Mitchell S. Cairo - 通讯作者:
Mitchell S. Cairo
Longitudinal, Real-World Data Reveal Treatment Effectiveness in Idiopathic Multicentric Castleman Disease and Support Current Treatment Guidelines
- DOI:
10.1182/blood-2022-170360 - 发表时间:
2022-11-15 - 期刊:
- 影响因子:
- 作者:
Sheila K Pierson;Mateo Sarmiento Bustamante;Joshua D Brandstadter;Daisy Alapat;Adam Bagg;Mary Jo Lechowicz;Gordan Srkalovic;Megan S. Lim;Frits van Rhee;David C Fajgenbaum - 通讯作者:
David C Fajgenbaum
Clinical Laboratory Mutation Analysis Performed on Tumor Biopsies from Patients with Relapsed/Refractory Aggressive B Cell Lymphoma Treated with Palliative-Intent Therapy
- DOI:
10.1182/blood-2022-165086 - 发表时间:
2022-11-15 - 期刊:
- 影响因子:
- 作者:
Danielle F Soberman;Jennifer J.D. Morrissette;Stephen J. Schuster;Sunita Dwivedy Nasta;James N. Gerson;Stefan K. Barta;Jakub Svoboda;Elise A. Chong;Megan S. Lim;Daniel J. Landsburg - 通讯作者:
Daniel J. Landsburg
The Diagnostic Utility of TRBC1 Immunohistochemistry in Mature T-Cell Lymphomas
TRBC1免疫组织化学在成熟T细胞淋巴瘤中的诊断效用
- DOI:
10.1016/j.modpat.2025.100725 - 发表时间:
2025-06-01 - 期刊:
- 影响因子:5.500
- 作者:
Ting Zhou;Rohan Sardana;Ozgur Can Eren;Melissa Pulitzer;Achim Jungbluth;Ahmet Dogan;Megan S. Lim - 通讯作者:
Megan S. Lim
The <em>NPM1</em>-<em>TYK2</em> Chimeric Fusion Promotes Activation of STAT Family Signaling, Skewing Towards Tfh Functional Subset Differentiation and Mature T-Cell Lymphomagenesis
- DOI:
10.1182/blood-2022-169494 - 发表时间:
2022-11-15 - 期刊:
- 影响因子:
- 作者:
Huang-Chang Liang;Richa Kapoor;Ozlem Onder;Kevin Dennis;Megan S. Lim;Kojo S.J. Elenitoba-Johnson - 通讯作者:
Kojo S.J. Elenitoba-Johnson
Megan S. Lim的其他文献
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{{ truncateString('Megan S. Lim', 18)}}的其他基金
Genomic biomarkers for cutaneous T-cell Lymphoma
皮肤 T 细胞淋巴瘤的基因组生物标志物
- 批准号:
10550139 - 财政年份:2022
- 资助金额:
$ 17.46万 - 项目类别:
Circulating biomarkers of ALK+ anaplastic large cell lymphoma
ALK 间变性大细胞淋巴瘤的循环生物标志物
- 批准号:
10703855 - 财政年份:2022
- 资助金额:
$ 17.46万 - 项目类别:
Circulating biomarkers of ALK+ anaplastic large cell lymphoma
ALK 间变性大细胞淋巴瘤的循环生物标志物
- 批准号:
10680558 - 财政年份:2022
- 资助金额:
$ 17.46万 - 项目类别:
Circulating biomarkers of ALK+ anaplastic large cell lymphoma
ALK 间变性大细胞淋巴瘤的循环生物标志物
- 批准号:
10298658 - 财政年份:2021
- 资助金额:
$ 17.46万 - 项目类别:
Circulating biomarkers of ALK+ anaplastic large cell lymphoma
ALK 间变性大细胞淋巴瘤的循环生物标志物
- 批准号:
10470371 - 财政年份:2021
- 资助金额:
$ 17.46万 - 项目类别:
Genomic biomarkers for cutaneous T-cell Lymphoma
皮肤 T 细胞淋巴瘤的基因组生物标志物
- 批准号:
10321292 - 财政年份:2020
- 资助金额:
$ 17.46万 - 项目类别:
Genomic biomarkers for cutaneous T-cell Lymphoma
皮肤 T 细胞淋巴瘤的基因组生物标志物
- 批准号:
9884667 - 财政年份:2020
- 资助金额:
$ 17.46万 - 项目类别:
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