Background & Aims

Somatic mosaicism, in which variants arise post-zygotically and are therefore not present in all cells in the body, may be an underestimated cause of colorectal cancer (CRC) and polyposis syndromes. We performed a systematic review to provide a comprehensive overview of somatic mosaicism in patients with CRC and polyposis syndromes.

Methods

We searched PubMed through March 2018 to identify reports of mosaicism in patients with CRC or polyposis syndromes. We divided the final set of studies into 3 subgroups describing APC mosaicism, mosaicism in other CRC susceptibility genes, and epigenetic mosaicism.

Results

Of the 232 articles identified in our systematic search, 46 met the criteria for further analysis. Of these, 35 studies described mosaic variants or epimutations in patients with CRC or polyposis syndromes. Nineteen studies described APC mosaicism, comprising a total of 57 patients. Six described mosaicism in genes associated with familial CRC syndromes, such as Lynch and Cowden syndromes. Ten studies described epigenetic mosaicism, sometimes resulting from a germline variant (such as deletion of EPCAM).

Conclusions

We found that somatic mosaicism is underdiagnosed but critical for determining the clinical management of patients with de novo polyposis who possibly carry mosaic APC variants, and present a decision tree for the clinical management of these patients. Mosaicism in genes associated with susceptibility to CRC contributes to development of other familial CRC syndromes. Heritable epigenetic mosaicism is likely underestimated and could have a dominant pattern of inheritance. However, the inheritance of primary mosaic epimutations, without an underlying genetic cause, is complex and not fully understood.

中文翻译：

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结直肠癌或息肉病综合征患者的嵌合：系统评价。

背景与目标

体细胞嵌合现象，其中变异出现在合子后，因此并不存在于身体的所有细胞中，可能是结直肠癌 (CRC) 和息肉病综合征的一个被低估的原因。我们进行了系统评价，以全面概述 CRC 和息肉病综合征患者的体细胞嵌合。

方法

我们检索了 PubMed 直至 2018 年 3 月，以确定 CRC 或息肉病综合征患者的嵌合体报告。我们将最后一组研究分为 3 个亚组，分别描述APC嵌合、其他 CRC 易感基因的嵌合和表观遗传嵌合。

结果

在我们系统搜索中确定的 232 篇文章中，46 篇符合进一步分析的标准。其中，35 项研究描述了 CRC 或息肉病综合征患者的镶嵌变异或表观突变。19 项研究描述了APC嵌合体，共包括 57 名患者。六个描述了与家族性 CRC 综合征相关的基因中的嵌合现象，例如 Lynch 和 Cowden 综合征。十项研究描述了表观遗传嵌合现象，有时是由种系变异（例如EPCAM缺失）引起的。

结论

我们发现体细胞嵌合未被诊断出来，但对于确定可能携带嵌合 APC 变异的新发息肉病患者的临床管理至关重要，并为这些患者的临床管理提供了一个决策树。与 CRC 易感性相关的基因嵌合有助于其他家族性 CRC 综合征的发展。可遗传的表观遗传嵌合体可能被低估，并且可能具有显性遗传模式。然而，在没有潜在遗传原因的情况下，原始镶嵌表观突变的遗传是复杂的并且尚未完全了解。