CLONING OF A LEIOMYOMA ASSOCIATED GENE ON CHROMOSOME 14

描述(申请人的描述)： 子宫肌瘤(UL)是人类最常见的肿瘤之一，是主要的 育龄妇女的公共卫生问题，也是最常见的 子宫切除术的适应症。这项提议的目的是孤立 并描述了一个与UL病理生物学有关的基因。建议数 研究集中在一个区域(染色体14q23-24)持续重排 约占UL总数的10%。为了定位克隆这个与子宫肌瘤相关的 奎德博士从一种子宫肌瘤细胞系中构建了一个粘粒文库 包含t(12；14)易位和孤立的宇宙 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该基因，分离其cDNA， 并研究其在UL及相关肿瘤中的表达和定位。 奎德医生是一位训练有素的临床诊断外科病理学家。 妇产科病理学方面的专业知识。他的主要兴趣是 女性生殖道平滑肌肿瘤的病理生物学 一条小路。虽然他以前有研究经验，但他的博士后 分子遗传学和细胞遗传学方面的培训与 他在细胞生物学和蛋白质生物化学方面的博士前训练 细胞外基质。额外的指导培训将使他能够建立 关于他已经获得的分子生物学技能，并提供了一个临界质量 向独立调查过渡所需的经验 在竞争激烈的环境中。该奖项提供的支持将 可与完整K08奖项的最后几年相媲美。他的终极目标 目标是建立独立的学术研究生涯调查 子宫平滑肌肿瘤的分子病理生物学及其临床应用 提高对本病的组织学诊断和临床治疗的认识 肿瘤。 莫顿博士的实验室是第一批克隆与子宫肌瘤相关的 基因(HMGI-C)通过定位方法获得，其独特之处在于它致力于 了解子宫肌瘤的分子遗传学。这项研究 病理学系和整个哈佛大学的环境 医学院社区是最高水平的，将提供博士。 Quade有足够的机会与经验丰富的分子遗传学家互动 当他完成训练的时候。

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.