GENETIC ANALYSIS USING THE GILDA RADNER REGISTRY

使用 GILDA RADNER 注册表进行遗传分析

• 批准号: 2390860
• 负责人: Jennifer Kelsey
• 金额: $ 33.08万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2390860
• 关键词: blood chemistry; brca gene; cancer registry /resource; cancer risk; family genetics; gene expression; gene mutation; hormone therapy; human genetic material tag; human subject; linkage mapping; neoplasm /cancer epidemiology; neoplasm /cancer genetics; oral contraceptives; ovariectomy; ovary neoplasms; questionnaires; women's health

Mutations of the BRCA1 gene are thought to be involved in at least 70% of families with excess incidence of cancers of the ovary and breast. Little is known about predisposing genes in the remaining breast/ovarian cancer families, or in families with excess ovarian cancer but little or no breast cancer. It is now feasible to identify other predisposing genes for ovarian cancer. Critical to this effort is DNA from many large ovarian cancer families. Because such families are rare, the Gilda Radner familial Ovarian Cancer Registry is an important resource for such study. The Registry, established at the Roswell Park Cancer Center in 1981, currently comprises some 1000 U.S. families containing at least two ovarian cancer diagnoses among first- or second-degree relatives. We propose to identify 100 of the most informative families to obtain blood and/or archival tissue specimens for genetic linkage analysis. We will address the following questions: i) What proportion of ovarian cancer families are due to the BRCA1 gene? ii) What epidemiologic features (e.g. mean age at onset, ethnicity, histologic subtype or malignant potential of tumor, other site-specific cancer occurrence) distinguish linked from unlinked families? iii) Do unlinked families show linkage to other loci? If, as seems almost certain, the BRCA1 gene is cloned within the project period, we also will examine the spectrum of other diseases associated with specific BRCA1 mutations, and assess which epidemiologic characteristics distinguish mutation carriers who develop cancer from those who do not. To accomplish these aims, we will select some 260 families containing three or more reported ovarian cancers and contact family members to complete the pedigrees and verify reported cancers against medical records. We then will select 100 of the most informative of these families and obtain blood and/or archival tissue specimens from affected members and first-degree relatives of affected members. Finally, we will isolate viable lymphocytes and DNA from blood samples and analyze the specimens for linkage and mutations in candidate genes. Use of this large registry to map predisposing genes for ovarian cancer and characterize families linked at different loci offers these benefits: it will identify women at genetically high risk who can be targeted for screening and intervention, and it will allow classification of ovarian cancers into genetic subtypes, thereby facilitating the study of etiologic factors and the planning of strategies for screening and prevention.

BRCA 1基因突变被认为与至少70%的 卵巢癌和乳腺癌发病率过高的家庭。 小 已知剩余的乳腺癌/卵巢癌的易感基因 或者卵巢癌过多但很少或没有卵巢癌的家庭， 乳腺癌 现在可以确定其他诱发基因 治疗卵巢癌 这项工作的关键是来自许多大型 卵巢癌家族 因为这样的家庭是罕见的，吉尔达拉德纳 家族性卵巢癌登记是此类研究的重要资源。 该登记处于1981年在罗斯韦尔公园癌症中心成立， 目前，美国约有1000个家庭， 一级或二级亲属中的卵巢癌诊断。 我们 建议确定100个信息量最大的家庭， 和/或用于遗传连锁分析的存档组织样本。 我们将 解决以下问题：i）卵巢癌的比例 BRCA 1基因是什么基因？ 2.有哪些流行病学特征（如： 平均发病年龄、种族、组织学亚型或恶性潜能 肿瘤，其他部位特异性癌症发生）区分与 没有联系的家庭？ （3）不连锁的家系是否与其他基因座连锁？ 如果BRCA 1基因在项目中被克隆， 在此期间，我们还将研究其他相关疾病的谱 与特定的BRCA 1突变，并评估哪些流行病学 突变携带者发展成癌症的特征， 那些不懂的人。 为了实现这些目标，我们将选择大约260个 包含三个或更多报告卵巢癌和接触的家庭 家庭成员完成谱系和核实报告的癌症 与医疗记录进行比对 然后我们将选出100个最具信息性的 并从这些家庭中获得血液和/或档案组织标本， 受影响的成员和受影响成员的一级亲属。 最后， 我们将从血液样本中分离出有活力的淋巴细胞和DNA， 用于候选基因中的连锁和突变的样本。使用本 大型登记处绘制卵巢癌的易感基因， 表征在不同位点连锁的家庭提供了这些好处：它 将确定哪些女性在遗传上有高风险， 筛查和干预，它将允许卵巢分类， 将癌症分为基因亚型，从而促进病因学研究 因素以及筛查和预防战略的规划。

项目成果

Primary ovarian dysgerminoma in a patient with a germline BRCA1 mutation.

患有生殖系 BRCA1 突变的原发性卵巢无性细胞瘤。

• DOI: 10.1097/00004347-200010000-00017
• 发表时间: 2000
• 期刊: International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists
• 作者: Werness,BA;Ramus,SJ;Whittemore,AS;Garlinghouse-Jones,K;Oakley-Girvan,I;DiCioccio,RA;Tsukada,Y;Ponder,BA;Piver,MS
• 通讯作者: Piver,MS

Analysis of BRCA1 and BRCA2 mutations in Hungarian families with breast or breast-ovarian cancer.

匈牙利乳腺癌或乳腺癌卵巢癌家族的 BRCA1 和 BRCA2 突变分析。

• 发表时间: 1997
• 期刊: American journal of human genetics
• 影响因子: 9.8
• 作者: Ramus,SJ;Kote-Jarai,Z;Friedman,LS;vanderLooij,M;Gayther,SA;Csokay,B;Ponder,BA;Olah,E
• 通讯作者: Olah,E

Screening for the BRCA1-ins6kbEx13 mutation: potential for misdiagnosis. Mutation in brief #964. Online.

筛查 BRCA1-ins6kbEx13 突变：误诊的可能性。

• DOI: 10.1002/humu.9493
• 发表时间: 2007
• 期刊: Human mutation
• 影响因子: 3.9
• 作者: Ramus,SusanJ;Harrington,PatriciaA;Pye,Carole;Peock,Susan;Cook,MargaretR;Cox,MarkJ;Jacobs,IanJ;DiCioccio,RichardA;Whittemore,AliceS;Piver,MSteven;EMBRACE;Easton,DouglasF;Ponder,BruceAJ;Pharoah,PaulDP;Gayther,SimonA
• 通讯作者: Gayther,SimonA

Histopathology of familial ovarian tumors in women from families with and without germline BRCA1 mutations.

来自有和没有种系 BRCA1 突变家族的女性的家族性卵巢肿瘤的组织病理学。

• 发表时间: 2000
• 期刊: Human pathology.
• 作者: Werness,BA;Ramus,SJ;Whittemore,AS;Garlinghouse-Jones,K;Oakley-Girvan,I;Dicioccio,RA;Tsukada,Y;Ponder,BA;Piver,MS
• 通讯作者: Piver,MS

BRCA1/2 mutation status influences somatic genetic progression in inherited and sporadic epithelial ovarian cancer cases.

• 发表时间: 2003-01
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: S. Ramus;P. Pharoah;P. Harrington;C. Pye;B. Werness;L. Bobrow;A. Ayhan;D. Wells;A. Fishman;M. Gore;R. Dicioccio;M. Piver;A. Whittemore;B. Ponder;S. Gayther