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（由申请人提供）：MYC 作为侵袭性非霍奇金淋巴瘤项目中的生物标志物摘要非霍奇金淋巴瘤 (NHL) 是最常见的血液恶性肿瘤，约占人类癌症的 4.6%，并导致美国所有癌症死亡的约 3.5%。 1975 年至 1991 年间，美国 NHL 的发病率增加了 80% 以上，是所有癌症中增幅最大的癌症之一（SEER 癌症统计回顾 1975-2004）。尽管 NHL 有 50 多种类型，但弥漫性大 B 细胞淋巴瘤 (DLBCL) 是最常见的，约占所有 NHL 的 35%。在美国，每年大约有十分之七的人受到 DLBCL 的影响。一半的 DLBCL 患者无法通过标准利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松 (R-CHOP) 疗法治愈。目前确定DLBLC预后最常用的工具是国际预后指数（IPI），该指数基于五项临床特征（患者年龄、肿瘤分期、血清乳酸脱氢酶浓度、体能状态和结外疾病部位数量）。然而，具有相同 IPI 评分的患者在生存方面表现出明显的变异性，这表明每个 IPI 类别中存在显着的残留异质性。通过易位、扩增或其他机制解除 MYC（编码 c-Myc 转录因子的基因）的管制对于 淋巴系统恶性肿瘤（包括 DLBCL）的发病机制。我们组建了一个由 25 个医疗中心组成的国际 DLBCL R-CHOP 联盟，并将自己打造为专门研究 DLBCL 生物标志物的领先团队。我们假设 MYC 是 DLBCL 预后和风险调整治疗的生物标志物。在本申请中，我们提出了三个目标，以确定 MYC 的遗传和非遗传改变在 DLBCL 预后和治疗中的潜力。在目标 1 中，我们将使用 3,000 个标本确定 MYC 在 DLBCL 预后中的综合作用。在目标 2 中，我们将确定具有 MYC 易位的 DLBCL 与没有 MYC 易位的 DLBCL 在基因表达和治疗反应方面是否有所不同。在目标 3 中，我们将确定 DLBCL 中 MYC CDS 和 3'UTR 突变的差异预后值的分子基础。