Genes in the Predisposition to Papillary Thyroid Carcinoma

甲状腺乳头状癌易感基因

• 批准号: 8505963
• 负责人: ALBERT DE LA CHAPELLE
• 金额: $ 37.82万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8505963
• 关键词: 12q14; 4q32; 8q24; Accounting; Affect; Alleles; Bioinformatics; Candidate Disease Gene; Case-Control Studies; Chromosomes; Collaborations; Data; Data Analyses; Databases; Development; Diagnostic; Disease Outcome; Elements; Enhancers; Epithelial; Etiology; Event; Family; Functional RNA; Gene Targeting; Genes; Genetic; Genetic Counseling; Genetic Predisposition to Disease; Genetic Variation; Genome; Genomics; Genotype; Heritability; Individual; Instruction; Lead; Length; Malignant Neoplasms; Malignant neoplasm of thyroid; Mediating; Medicine; Methodology; Methods; Molecular; Molecular Genetics; Morbidity - disease rate; Mutate; Mutation; Nature; Nucleotides; Outcome; Outcomes Research; Papillary thyroid carcinoma; Pathogenesis; Pathway interactions; Patients; Penetrance; Pharmacotherapy; Population Study; Predisposition; Price; Progress Reports; Research; Risk; Risk Assessment; Role; Sampling; Signal Pathway; Stratification; Susceptibility Gene; Technology; Testing; Thyroid Gland; Tissues; Transcriptional Regulation; Untranslated RNA; Variant; base; cancer initiation; deep sequencing; design; disease-causing mutation; evidence base; exome; falls; gene function; genetic linkage analysis; genetic risk assessment; genetic variant; genome sequencing; genome wide association study; improved; insight; kindred; member; mortality; novel; positional cloning; research study; screening; therapeutic target

The broad, long term objective of this project is to reduce morbidity and mortality caused by papillary thyroid carcinoma (PTC) which accounts for - 80% of all thyroid cancer. PTC displays remarl<ably high heritability suggesting the existence of genes that when mutated predispose to PTC. The traditional way of searching for such genes is by linkage analysis in families with multiple affected individuals. Despite vigorous world-wide research this approach has yielded modest results in that only 3 genes have been detected that in all lil<elihood cause PTC, and the total number of individuals affected by these genes is minimal. This has led to the hypothesis that the putative culpable genes are either common but of extremely low effect size (penetrance) or might be of higher penetrance but rare or super rare. Our genome wide association studies (GWAS) have begun to sustain this hypothesis in that several loci with low effect size have been detected. We are focusing on rare higher penetrance genes in families in this Project based on findings from the first cycle of this POl. In particular, a novel type of gene, long intergenic noncoding RNA (lincRNAs) appears to underlie at least some of these susceptibility loci. We are presently applying whole genome sequencing to members of affected families in search of further culpable genes. At least one case of an ultra rare high penetrance gene has been detected in this way, and with improvements in technology this avenue likely will lead to a fuller understanding of the genetic predisposition to PTC.

该项目的广泛长期目标是降低乳头状的发病率和死亡率 甲状腺癌（PTC）占所有甲状腺癌的80％。 PTC显示Remarl <非常高 遗传力表明存在突变为PTC时存在基因。传统的方式 搜索此类基因是通过在具有多个受影响个体的家庭中进行连锁分析。尽管 全球范围内的剧烈研究这种方法产生了适度的结果，因为只有3个基因是 检测到在所有lil <Elihood中都会导致PTC，并且受这些基因影响的个体的总数为 最小。这导致了以下假设：假定的可抑制基因是常见的，但 效果的大小极低（渗透率），或者可能具有更高的渗透率，但罕见或超级罕见。我们的 基因组广泛的关联研究（GWAS）已开始维持这一假设，因为 检测到低效应大小。我们专注于家庭中罕见的较高的外渗基因 项目基于此POL的第一个周期的发现。特别是一种新型的基因，长基因间 非编码RNA（LincrNA）似乎至少是其中一些易感基因座。我们现在是 将整个基因组测序应用于受影响家族的成员，以寻求进一步的基因。 以这种方式检测到至少一种超罕见的高渗透基因，并在 技术的进步这一途径可能会导致对遗传的全面了解 PTC的易感性。