Genes in the Predisposition to Papillary Thyroid Carcinoma

该项目广泛的长期目标是减少乳头状瘤引起的发病率和死亡率。 甲状腺癌（PTC）占所有甲状腺癌的80%。PTC显示器的显示温度非常高 遗传性表明存在突变时易患PTC的基因。的传统方式 通过在具有多个受影响个体的家庭中进行连锁分析来寻找这样的基因。尽管 这种方法在全世界范围内进行了积极的研究，结果并不多，因为只有3个基因被 检测到所有导致PTC的基因，受这些基因影响的个体总数是 最小的这导致了一种假设，即假定的罪魁祸首基因要么是常见的， 极低的效应量（极低的效应量）或可能具有较高的极低的效应量，但罕见或超级罕见。我们 全基因组关联研究（GWAS）已经开始支持这一假设，因为几个基因座具有 已检测到低效应量。我们关注的是这个家族中罕见的高突变率基因。 基于本项目第一轮研究结果的项目。特别是，一种新型基因，长基因间隔， 非编码RNA（lincRNA）似乎是这些易感性基因座中的至少一些的基础。我们目前正在 对受影响的家庭成员进行全基因组测序，以寻找更多的罪魁祸首基因。 至少有一例超罕见的高突变率基因已经以这种方式被发现， 技术的进步，这条途径可能会导致对遗传的更全面的理解。 易患PTC。

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.