A Mutational Model for Childhood Cancer

儿童癌症的突变模型

• 批准号: 7080077
• 负责人: LOUISE C STRONG
• 金额: $ 284.84万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7080077
• 关键词: cancer risk; clinical research; family genetics; gene mutation; neoplasm /cancer genetics; pediatric neoplasm /cancer

DESCRIPTION (provided by applicant): The overall goal of the program is to identify genes that predispose to childhood cancer, the molecular pathways to tumor development, and the clinical implications. We have focused on two model familial syndromes of childhood and adolescent cancers, sarcomas and Li Fraumeni Syndrome (LFS) and its variants, and Wilms' tumor of the kidney. We have developed a multidisciplinary program to investigate genetic susceptibility to childhood and associated cancer using integrated technology of genetic epidemiology, molecular genetics and genomics applied to the rich resources of cancer prone families and mouse models developed in this program. The hypotheses are based on a multi-stage model for cancer. For each tumor type, genetic loci have been identified that may be altered both as germline mutations and as tumor-specific mutations. There is also significant evidence for additional cancer susceptibility genes and risk modifiers, including an effect of generation, at least for LFS. The underlying themes of the program include identification of the underlying cancer susceptibility genes and risk modifiers, analysis of germline and somatic mutations by type and mechanism, determination of the molecular genetic anatomy of the tumors, development of animal models for human cancer susceptibility syndromes, determination of the role of telomere function in cancer risk in LFS and mouse models, and determination of the implications of germline mutations for the patients and their families. The findings from this program should provide insights into the mechanisms of carcinogenesis as well as guidelines for clinical programs for patients at high risk of cancer.

描述(由申请人提供)：该计划的总体目标是确定儿童癌症的易感基因，肿瘤发生的分子途径，以及临床意义。我们聚焦于儿童和青少年癌症的两个典型家族性综合征，肉瘤和Li Fraumeni综合征(LFS)及其变异体，以及肾母细胞瘤。我们开发了一个多学科计划，利用遗传流行病学、分子遗传学和基因组学的集成技术，研究儿童和相关癌症的遗传易感性，并将其应用于癌症易感家庭的丰富资源和在该计划中开发的小鼠模型。这些假设是基于癌症的多阶段模型。对于每一种肿瘤类型，已经确定了可以改变为种系突变和肿瘤特异性突变的遗传位点。也有重要的证据表明存在其他癌症易感基因和风险修饰物，包括世代效应，至少对LFS是这样。该计划的基本主题包括识别潜在的癌症易感基因和风险修饰物，按类型和机制分析胚系和体细胞突变，确定肿瘤的分子遗传解剖学，建立人类癌症易感综合征的动物模型，确定端粒功能在LFS和小鼠模型中的癌症风险中的作用，以及确定胚系突变对患者及其家人的影响。该项目的研究结果将为癌症高危患者提供致癌机制方面的见解，并为临床项目提供指导。