Genetic Alterations in Families with Multiple Lymphomas

多发性淋巴瘤家族的基因改变

• 批准号: 7922785
• 负责人: Jennifer R Brown
• 金额: $ 6.91万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7922785
• 关键词: Adult Lymphoma; Biological; Candidate Disease Gene; Case Study; Cells; Characteristics; Clinic; Clinical; Dana-Farber Cancer Institute; Data; Development; Ensure; Etiology; Extended Family; Faculty; Family; First Degree Relative; Follicular Lymphoma; Gene Expression; Genetic; Genetic Predisposition to Disease; Germinal Center B-Lymphocyte; Goals; Hodgkin Disease; Immunologic Deficiency Syndromes; Incidence; Investigation; Joints; Lead; Loss of Heterozygosity; Lymphoma; Lymphoproliferative Disorders; Malignant - descriptor; Malignant Neoplasms; Methods; Molecular; Molecular Biology; Mononuclear; Mutation; Non-Hodgkin' s Lymphoma; Patients; Pattern; Peripheral Blood Lymphocyte; Play; Predisposition; Prevention; Radiation therapy; Research; Research Proposals; Resources; Role; Screening procedure; Serum; Site; Source; Testing; Tissue Banking; Tissue Banks; Tissues; Training; Tumor Tissue; United States; base; career; genetic linkage analysis; large cell Diffuse non-Hodgkin' s lymphoma; medical schools; novel; programs; repository; research study

DESCRIPTION (provided by applicant): Non-Hodgkin's lymphomas (NHLs) are the 5th most common malignancy in the United States, with an incidence that has increased significantly over the last decade. Preliminary data obtained from Adult Lymphoma clinic at DFCI, as well as from Hodgkin's lymphoma patients treated at the Harvard Joint Center for Radiation Therapy (JCRT), show that 6-9% of these patients have a first-degree relative who also has a lymphoproliferative disorder. The goals of this research proposal are to systematically identify and characterize the subset of lymphomas associated with apparent familial predisposition and to determine whether their genetic basis can be identified. The Specific Aims of this project are: (1) to identify families with at least two first-degree relatives with lymphoproliferative malignancy and establish a data and tissue bank including serum, peripheral blood lymphocytes, germline DMA, and tumor tissue; (2) to investigate whether familial lymphomas have characteristic sites of loss of heterozygosity and to attempt to identify candidate genes within those regions; (3) to investigate whether familial lymphomas have characteristic patterns of global gene expression; (4) to perform a linkage analysis to identify candidate genes in the germline that may predispose to lymphoma development. These novel experiments should illuminate the biological underpinnings of familial lymphoma, which should in turn lead to targeted therapies and possibly methods of screening or prevention. This project will enable the candidate to use her scientific training in molecular biology to develop an academic career in clinical / translational investigation in lymphoma, applying novel scientific discoveries to the clinic. The research will be conducted primarily at Dana-Farber Cancer Institute and Harvard Medical School, where extensive clinical, scientific and faculty resources are available to ensure the completion of the project.

描述（由申请人提供）：非霍奇金的淋巴瘤（NHL）是美国第五大最常见的恶性肿瘤，在过去十年中的发病率显着增加。从DFCI的成人淋巴瘤诊所获得的初步数据，以及在哈佛大学放射治疗中心（JCRT）治疗的Hodgkin淋巴瘤患者（JCRT），这些患者中有6-9％的患者具有一级亲戚，他们也具有淋巴细胞增生性的。紊乱。这项研究建议的目标是系统地识别和表征与明显家族性倾向相关的淋巴瘤的子集，并确定是否可以鉴定其遗传基础。该项目的具体目的是：（1）确定至少两个具有淋巴增生性恶性肿瘤的一级亲戚的家庭，并建立数据和组织库，包括血清，外周血淋巴细胞，种系DMA和肿瘤组织； （2）研究家族性淋巴瘤是否具有杂合性丧失的特征部位，并试图鉴定这些区域内的候选基因； （3）研究家族性淋巴瘤是否具有全球基因表达的特征模式； （4）进行连锁分析以鉴定可能易感淋巴瘤发育的种系中的候选基因。这些新颖的实验应阐明家族性淋巴瘤的生物基础，这反过来又应导致靶向疗法，并可能是筛查或预防的方法。该项目将使候选人能够利用她在分子生物学方面的科学培训来发展淋巴瘤临床 /转化研究的学术生涯，并将新颖的科学发现应用于诊所。这项研究将主要在达纳 - 法伯癌症研究所和哈佛医学院进行，那里有广泛的临床，科学和教职资源，以确保项目的完成。

项目成果

Ibrutinib (PCI-32765), the first BTK (Bruton's tyrosine kinase) inhibitor in clinical trials.

• DOI: 10.1007/s11899-012-0147-9
• 发表时间: 2013-03
• 期刊: CURRENT HEMATOLOGIC MALIGNANCY REPORTS
• 影响因子: 2.9
• 作者: Brown, Jennifer R.

Susceptibility loci associated with specific and shared subtypes of lymphoid malignancies.

• DOI: 10.1371/journal.pgen.1003220
• 发表时间: 2013
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Vijai J;Kirchhoff T;Schrader KA;Brown J;Dutra-Clarke AV;Manschreck C;Hansen N;Rau-Murthy R;Sarrel K;Przybylo J;Shah S;Cheguri S;Stadler Z;Zhang L;Paltiel O;Ben-Yehuda D;Viale A;Portlock C;Straus D;Lipkin SM;Lacher M;Robson M;Klein RJ;Zelenetz A;Offit K
• 通讯作者: Offit K

Inherited predisposition to chronic lymphocytic leukemia.

• DOI: 10.1586/17474086.1.1.51
• 发表时间: 2008-10
• 期刊: Expert review of hematology
• 影响因子: 2.8
• 作者: Brown JR

Phase II study of dasatinib in relapsed or refractory chronic lymphocytic leukemia.

• DOI: 10.1158/1078-0432.ccr-10-2879
• 发表时间: 2011-05-01
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Amrein PC;Attar EC;Takvorian T;Hochberg EP;Ballen KK;Leahy KM;Fisher DC;Lacasce AS;Jacobsen ED;Armand P;Hasserjian RP;Werner L;Neuberg D;Brown JR
• 通讯作者: Brown JR

Genetic variation in DNA repair pathways and risk of non-Hodgkin's lymphoma.

• DOI: 10.1371/journal.pone.0101685
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Rendleman J;Antipin Y;Reva B;Adaniel C;Przybylo JA;Dutra-Clarke A;Hansen N;Heguy A;Huberman K;Borsu L;Paltiel O;Ben-Yehuda D;Brown JR;Freedman AS;Sander C;Zelenetz A;Klein RJ;Shao Y;Lacher M;Vijai J;Offit K;Kirchhoff T
• 通讯作者: Kirchhoff T