Drivers and implications of lineage-specific cancer-related mutations in human pluripotent and adult stem cells

人类多能干细胞和成体干细胞中谱系特异性癌症相关突变的驱动因素和意义

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Abstract

Human pluripotent stem cells (PSCs) are known to harbor mutations in tumor-associated genes, and here we aim to examine the status of adult stem cells (ASCs). We thus identify cancer-related mutations in 18% of about 600 mesenchymal stem cell samples, and in 41% of about 200 neural stem cell (NSC) samples. We show a lineage-specific profile of cancer-related genes, demonstrating that TP53 is a central mutated gene in human PSCs but not in mesenchymal or NSCs. We suggest that the lineage-specificity of tumor-associated genes correlates with their expression levels and with tumor-specific mutations in patients. We also show the consequences of mutations in oncogenes and tumor suppressor genes on the transcriptome of each specific stem cell lineage. We therefore propose a categorization of these mutated samples for further appreciation of their severity and emphasize the importance of genetic screening in pluripotent and ASC lines.

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