A Mutational Model for Childhood Cancer

儿童癌症的突变模型

• 批准号: 7915079
• 负责人: LOUISE C STRONG
• 金额: $ 71.65万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7915079
• 关键词: Mutational; Model; Childhood; 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易感儿童癌症的基因，肿瘤发育的分子途径以及临床意义。我们专注于两种模型的儿童和青春期癌症，肉瘤和李弗劳梅尼综合征（LFS）及其变体的综合症，以及威尔姆斯的肾脏肿瘤。我们已经开发了一项多学科计划，使用遗传流行病学，分子遗传学和基因组学的综合技术调查了对儿童期和相关癌症的遗传敏感性，该技术应用于该计划中开发的癌症易于癌症的丰富资源和小鼠模型。这些假设基于癌症的多阶段模型。对于每种肿瘤类型，已经鉴定出遗传基因座可能会因种系突变和肿瘤特异性突变而改变。也有大量证据表明，至少在LFS中，包括产生的额外癌症敏感性基因和风险修饰剂（包括发电的效果）。该计划的基本主题包括鉴定潜在的癌症敏感性基因和风险修饰剂，通过类型和机制对种系和体细胞突变的分析，确定肿瘤的分子遗传解剖结构，动物模型的发展人类癌敏感性综合症的动物模型，在LFS和小鼠模型中的伸缩率在癌症风险中的作用以及确定其在癌症风险中的作用以及确定的生物以及确定和确定的生产范围。该计划的发现应提供有关癌变机制的见解，以及针对高风险患癌症患者的临床计划的指南。