The discovery that rare POT1 variants are associated with extremely long telomeres and increased cancer predisposition has provided a framework to revisit the relationship between telomere length and cancer development. Telomere shortening is linked with increased risk for cancer. However, over the past decade, there is increasing evidence to show that extremely long telomeres caused by mutations in shelterin components (POT1, TPP1, and RAP1) also display an increased risk of cancer. Here, we will review current knowledge on germline mutations of POT1 identified from cancer-prone families. In particular, we will discuss some common features presented by the mutations through structure-function studies. We will further provide an overview of how POT1 mutations affect telomere length regulation and tumorigenesis.

中文翻译：

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癌症中端粒过长的谜团：从罕见的人类 POT1 变异中吸取的教训。

罕见的 POT1 变异与极长的端粒和增加的癌症易感性相关的发现为重新审视端粒长度与癌症发展之间的关系提供了一个框架。端粒缩短与癌症风险增加有关。然而，在过去十年中，越来越多的证据表明，由外壳素成分（POT1、TPP1 和 RAP1）突变引起的极长端粒也会增加患癌症的风险。在这里，我们将回顾目前关于从易患癌症家族中鉴定的 POT1 种系突变的知识。特别是，我们将通过结构功能研究讨论突变呈现的一些共同特征。我们将进一步概述 POT1 突变如何影响端粒长度调节和肿瘤发生。