张贝 (2023-03-31 22:30):
#paper RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues. Science. 2019 Jun 7;364(6444):eaaw0726.doi: 10.1126/science.aaw0726. 体细胞突变是如何在正常细胞中积累的,目前尚不清楚。本文通过对来自29个正常组织的6700个样本的RNA测序数据的综合分析揭示了多个体细胞变异,表明在许多正常组织中可以发现宏观克隆。本文证实阳光照射的皮肤、食道和肺比其他测试组织有更高的突变负担,这表明环境因素可以促进体细胞嵌合。突变负担与年龄和组织特异性细胞增殖率相关,强调突变随着时间和细胞分裂数量的增加而积累。最后,作者发现正常组织中存在已知癌症基因和热点突变。本研究提供了人体组织中宏观克隆扩增的广阔视野,从而作为将克隆扩增与环境因素、衰老和疾病风险联系起来的基础
RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues
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Abstract:
How somatic mutations accumulate in normal cells is poorly understood. A comprehensive analysis of RNA sequencing data from ~6700 samples across 29 normal tissues revealed multiple somatic variants, demonstrating that macroscopic clones can be found in many normal tissues. We found that sun-exposed skin, esophagus, and lung have a higher mutation burden than other tested tissues, which suggests that environmental factors can promote somatic mosaicism. Mutation burden was associated with both age and tissue-specific cell proliferation rate, highlighting that mutations accumulate over both time and number of cell divisions. Finally, normal tissues were found to harbor mutations in known cancer genes and hotspots. This study provides a broad view of macroscopic clonal expansion in human tissues, thus serving as a foundation for associating clonal expansion with environmental factors, aging, and risk of disease.
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