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CLONING OF A LEIOMYOMA ASSOCIATED GENE ON CHROMOSOME 14

14 号染色体上平滑肌瘤相关基因的克隆

基本信息

批准号：
2895751
负责人：
BRADLEY J QUADE
金额：
$ 9.18万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-05-05 至 2001-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (Applicant's Description): Uterine leiomyomata (UL) are one of the most common human neoplasms, a major public health problem for women of reproductive age, and the most frequent indication for hysterectomy. The objective of this proposal is to isolate and characterize a gene involved in the pathobiology of UL. The proposed studies focus on a region (chromosome 14q23-24) consistently rearranged in about 10 percent of all UL. To positionally clone this leiomyoma-associated gene, Dr. Quade has constructed a cosmid library from a leiomyoma cell line containing the t(12;14) translocation and isolated cosmids containing this rearranged region. Under the sponsorship of Dr. Cynthia Morton, he will identify the gene by exon trapping and sample sequencing, isolate its cDNA, and characterize its expression and localization in UL and related tumors. Dr. Quade is a well-trained diagnostic surgical pathologist with clinical expertise in gynecological and obstetrical pathology. His primary interest is the pathobiology of smooth muscle tumors of the female reproductive tract. Although he has previous research experience, his postdoctoral training in molecular genetics and cytogenetics was a major departure from his predoctoral training in the cell biology and protein biochemistry of the extracellular matrix. Additional mentored training will allow him to build on the molecular biology skills he has acquired and provide a critical mass of experience necessary to make the transition to independent investigation in a highly competitive environment. Support provided by this award would be comparable to the final years of a full term K08 award. His ultimate goal is to establish an independent academic research career investigating the molecular pathobiology of uterine smooth muscle tumors and to apply that knowledge to improving histologic diagnosis and clinical treatment of these tumors. Dr. Morton's laboratory was among the first to clone a leiomyoma-associated gene (HMGI-C) by positional methods and is unique in its commitment to understanding the molecular genetics of uterine leiomyomata. The research environment within the Pathology Department and throughout the Harvard Medical School community is of the highest caliber and will provide Dr. Quade ample opportunities to interact with experienced molecular geneticists as he completes his training.

描述（申请人的描述）：子宫平滑肌瘤（UL）是最常见的人类肿瘤之一，是一种主要的育龄妇女面临的公共卫生问题，也是最常见的问题子宫切除术的指征。该提案的目的是隔离并描述了参与 UL 病理学的基因。拟议的研究重点是一个不断重排的区域（染色体 14q23-24）约占所有 UL 的 10%。为了定位克隆这种与平滑肌瘤相关的基因，Quade 博士从平滑肌瘤细胞系构建了粘粒文库含有 t(12;14) 易位和含有该易位的分离粘粒重新排列的区域。在辛西娅·莫顿博士的赞助下，他将通过外显子捕获和样品测序鉴定基因，分离其cDNA，并表征其在 UL 和相关肿瘤中的表达和定位。 Quade 博士是一位训练有素的诊断外科病理学家，具有临床经验妇科和产科病理学专业知识。他的主要兴趣是女性生殖系统平滑肌肿瘤的病理学道。虽然他之前有研究经验，但他的博士后分子遗传学和细胞遗传学的培训与他在细胞生物学和蛋白质生物化学方面接受过博士前培训细胞外基质。额外的指导培训将使他能够建立论他所获得的分子生物学技能并提供了临界质量过渡到独立调查所需的经验在竞争激烈的环境中。该奖项提供的支持将相当于全学期 K08 奖项的最后几年。他的终极目标是建立独立的学术研究职业调查子宫平滑肌肿瘤的分子病理学及其应用提高这些疾病的组织学诊断和临床治疗的知识肿瘤。莫顿博士的实验室是最早克隆与平滑肌瘤相关的实验室之一基因（HMGI-C）通过定位方法，其独特之处在于它致力于了解子宫平滑肌瘤的分子遗传学。研究病理学系和整个哈佛大学的环境医学院社区具有最高水平，并将提供博士。与经验丰富的分子遗传学家互动的充足机会当他完成训练时。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

HMGIC expression in human adult and fetal tissues and in uterine leiomyomata

DOI：
10.1002/(sici)1098-2264(199908)25:4<316::aid-gcc2>3.3.co;2-s
发表时间：
1999-08-01
期刊：
GENES CHROMOSOMES & CANCER
影响因子：
3.7
作者：
Gattas, GJF;Quade, BJ;Morton, CC
通讯作者：
Morton, CC

Frequent loss of heterozygosity for chromosome 10 in uterine leiomyosarcoma in contrast to leiomyoma.

与平滑肌瘤相比，子宫平滑肌肉瘤中 10 号染色体杂合性频繁丢失。

DOI：
10.1016/s0002-9440(10)65342-4
发表时间：
1999
期刊：
The American journal of pathology
影响因子：
0
作者：
Quade,BJ;Pinto,AP;Howard,DR;Peters3rd,WA;Crum,CP
通讯作者：
Crum,CP

Fusion transcripts involving HMGA2 are not a common molecular mechanism in uterine leiomyomata with rearrangements in 12q15.

DOI：
发表时间：
2003-03
期刊：
Cancer research
影响因子：
11.2
作者：
B. Quade;S. Weremowicz;David M. Neskey;R. Vanni;C. Ladd;P. Dal Cin;C. Morton
通讯作者：
B. Quade;S. Weremowicz;David M. Neskey;R. Vanni;C. Ladd;P. Dal Cin;C. Morton

Expression of HMGIY in three uterine leiomyomata with complex rearrangements of chromosome 6.

HMGIY 在具有 6 号染色体复杂重排的三个子宫平滑肌瘤中的表达。

DOI：
10.1016/s0165-4608(99)00054-0
发表时间：
1999
期刊：
Cancer genetics and cytogenetics
影响因子：
0
作者：
Sornberger,KS;Weremowicz,S;Williams,AJ;Quade,BJ;Ligon,AH;Pedeutour,F;Vanni,R;Morton,CC
通讯作者：
Morton,CC

Granulocyte macrophage colony-stimulating factor in adenomyosis and autologous endometrium.