CLONING OF A LEIOMYOMA ASSOCIATED GENE ON CHROMOSOME 14

描述（申请人描述）： 子宫平滑肌瘤（UL）是人类最常见的肿瘤之一，也是一种主要的肿瘤 育龄妇女的公共卫生问题，以及最常见的 子宫切除适应症。 这项提案的目的是隔离 并表征参与UL病理生物学的基因。 拟议 研究集中在一个区域（染色体14 q23 -24）一致重排， 约占所有UL的10%。 为了定位克隆这个平滑肌瘤相关的 Quade博士从平滑肌瘤细胞系中构建了一个粘粒文库， 含有t（12;14）易位的重组蛋白和含有该重组蛋白的分离的重组蛋白 重组区 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， 并表征其在UL和相关肿瘤中的表达和定位。 博士Quade是一位训练有素的诊断外科病理学家， 妇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。 虽然他有以前的研究经验，他的博士后 分子遗传学和细胞遗传学的培训是一个重大的偏离， 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 他所获得的分子生物学技能，并提供了一个临界质量， 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 可与K 08全任期奖的最后几年相媲美。 他的最终 目标是建立一个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，并应用 对提高组织学诊断和临床治疗的认识 肿瘤的 博士莫顿的实验室是最早克隆出平滑肌瘤相关基因的实验室之一。 基因（HMGI-C）的定位方法，是独特的，在其承诺， 了解子宫平滑肌瘤的分子遗传学。 研究 在病理学系和整个哈佛的环境 医学院社区是最高素质的，并将提供博士。 Quade有充足的机会与经验丰富的分子遗传学家互动 完成他的训练。

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.