Genes in the Predisposition to Papillary Thyroid Carcinoma

该项目的广泛、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显示再融资能力很高 遗传性提示存在突变时易患PTC的基因。传统的方式是 在有多个受影响个体的家庭中，通过连锁分析来寻找这样的基因。尽管 这种方法在世界范围内进行了积极的研究，只取得了有限的结果，因为只有3个基因 检测到导致PTC的所有基因，以及受这些基因影响的个体总数为 最低限度。这导致了一种假设，即假定的罪魁祸首基因要么是常见的，要么是 极低的效果大小(外显度)，或者可能具有较高的外显率，但很罕见或超罕见。我们的 全基因组关联研究已经开始支持这一假说，因为有几个基因座与 检测到了较低的效应尺寸。我们关注的是这个家族中罕见的高外显性基因 基于本极地第一个周期的调查结果的项目。特别是一种新类型的基因，长基因间 非编码RNA(LincRNAs)似乎至少是这些易感基因座的基础。我们目前正在 将全基因组测序应用于受影响家庭的成员，以寻找进一步的罪魁祸首基因。 至少有一例超罕见的高外显性基因已经通过这种方式被检测到，并且 技术的改进这一途径可能会导致对基因的更全面的理解 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.