MYC as a Biomarker in Aggressive Non-Hodgkin Lymphoma

MYC 作为侵袭性非霍奇金淋巴瘤的生物标志物

• 批准号: 10019120
• 负责人: Yong Li
• 金额: $ 38.5万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10019120
• 关键词: 3' Untranslated Regions; 5' Untranslated Regions; Accounting; Adjuvant; Affect; Age; Animal Model; BCL2 gene; Belief; Binding Sites; Biological; Biological Assay; Biological Markers; Biological Process; Biology; Cancer Etiology; Cancer Prognosis; Categories; Cell Line; Cells; Cessation of life; Characteristics; Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; Code; Consensus; Cyclophosphamide; DNA Binding Domain; Diagnosis; Disease; Doxorubicin; Exhibits; Exons; Extranodal; Gene Expression; Gene Expression Profiling; Gene Mutation; Genes; Genetic; Goals; Guide RNA; Hematologic Neoplasms; Heterogeneity; Human; Immunodeficient Mouse; Incidence; Institution; International; International Prognostic Index; Lactate Dehydrogenase; Lymphoma; MYC gene; Malignant Neoplasms; Malignant lymphoid neoplasm; Medical center; Messenger RNA; MicroRNAs; Modeling; Molecular; Mus; Mutation; Non-Hodgkin' s Lymphoma; Nonsense Codon; Oncogenic; Oncoproteins; Pathogenesis; Patients; Performance Status; Phenotype; Play; Prednisone; Prognostic Marker; Proteins; Proto-Oncogene Proteins c-myc; Radiation; Radiation therapy; Regimen; Research; Residual state; Risk; Role; Serum; Site; Specimen; Stratification; Subgroup; Survival Analysis; Therapy Clinical Trials; Tumor stage; Tumorigenicity; United States; Vincristine; base; c-myc Genes; cancer risk; cancer statistics; chemotherapy; clinical application; cohort; differential expression; drug development; genome editing; improved; large cell Diffuse non-Hodgkin' s lymphoma; non-genetic; outcome forecast; overexpression; prognostic; prognostic value; protein expression; public health relevance; radiation response; rituximab; tool; transcription factor; transcriptome; treatment response; tumor growth

 DESCRIPTION (provided by applicant): MYC as a Biomarker in Aggressive Non-Hodgkin Lymphoma Project Abstract Non-Hodgkin lymphoma (NHL) is the most common hematological malignancy, constituting about 4.6% of human cancers and causing about 3.5% of all cancer deaths in the United States. The incidence of NHL has increased by more than 80% between 1975 and 1991 in the United States - one of the largest increases of any cancer (SEER Cancer Statistics Review 1975-2004). Although there are more than 50 types of NHLs, diffuse large B cell lymphoma (DLBCL) is the most common, accounting for approximately 35 percent of all NHLs. In the United States, DLBCL affects about 7 out of 100,000 people each year. Half of DLBCL patients cannot be cured with the standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. 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 patients with identical IPI scores exhibit marked variability in survival, suggesting the presence of significant residual heterogeneity within each IPI category. Deregulation of MYC, the gene that encodes the c-Myc transcription factor, through translocation, amplification, or other mechanisms is important in the pathogenesis of lymphoid malignancies, including DLBCL. We have assembled an International DLBCL R-CHOP Consortium with 25 medical centers and have established ourselves as a leading team specializing in DLBCL biomarkers. We hypothesize that MYC is a biomarker for DLBCL prognosis and risk-adjusted therapies. In this application, we propose three aims to ascertain the potential of genetic and non-genetic alteration of MYC in DLBCL prognosis and therapy. In Aim 1, we will determine the comprehensive role of MYC in DLBCL prognosis using 3,000 specimens. In Aim 2, we will determine whether DLBCL with MYC translocation differs from those without MYC translocation in gene expression and treatment response. In Aim 3, we will determine the molecular basis of differential prognostic values of MYC CDS and 3'UTR mutations in DLBCL.

 描述（由适用提供）：MYC作为侵略性非霍奇金淋巴瘤项目的生物标志物摘要非霍奇金淋巴瘤（NHL）是最常见的血液系统恶性肿瘤，管理约4.6％的人类癌症，并在美国所有癌症死亡中造成约3.5％的癌症。在1975年至1991年之间，NHL的事件增长了80％以上，这是任何癌症的最大增长之一（Seer Cancer Statistics评论1975- 2004年）。尽管有50种以上的NHL，但最常见的弥漫性大B细胞淋巴瘤（DLBCL）是所有NHL的35％。在美国，DLBCL每年影响100,000人中约有7人。一半的DLBCL患者不能用标准的利妥昔单抗，环磷酰胺，阿霉素，长春新碱和泼尼松（R-Chop）治疗治愈。目前，确定DLBLC提示的最常见工具是国际预后指数（IPI），该指数基于五个临床特征（患者年龄，肿瘤阶段，血清乳酸脱氢酶浓度，性能状态，表现状态和外疾病外疾病部位的数量）。然而，IPI评分相同的患者暴露了生存的明显差异，这表明每个IPI类别中存在明显的残留异质性。通过易位，放大或其他机制对MYC的放松调节，编码C-MYC转录因子的基因在 淋巴性恶性肿瘤的发病机理，包括DLBCL。我们已经组建了一个国际DLBCL R-CHOP财团，并建立了25个医疗中心，并将自己确立为专门从事DLBCL生物标志物的领先团队。我们假设MYC是DLBCL预后和风险调整疗法的生物标志物。在此应用中，我们提出三个旨在确定MYC在DLBCL预后和治疗中遗传和非遗传改变的潜力。在AIM 1中，我们将使用3,000个标本来确定MYC在DLBCL预后中的全面作用。在AIM 2中，我们将确定在基因表达和治疗反应中没有MYC易位的DLBCL是否与没有MYC易位的DLBCL不同。在AIM 3中，我们将确定DLBCL中MYC CD和3'UTR突变的差异预后值的分子基础。