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

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.