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Background  In terms of biological behavior, gene regulation, or signaling pathways, there is a certain similarity between tumorigenesis and embryonic development of humans. Three germ layer structure exhibits the distinct ability to form specific tissues and organs.    Methods  The present study set out to investigate the genetic mutation characteristics of germ layer differentiation-related genes using the tumor cases of the cancer genome atlas (TCGA) database.    Results  These tumor samples were divided into three groups, including the ectoderm, mesoderm, and endoderm. Children cases less than 9 years old accounted for a larger proportion for the cases in the ectoderm and mesoderm groups; whereas the middle-aged and elderly individuals (from 50 to 89 years old) were more susceptible to tumors of endoderm. There was a better prognosis for the cases of mesoderm, especially the male with the race of White, compared with the other groups. A missense mutation was frequently detected for the cases of ectoderm and endoderm, while deletion mutation was common for that of mesoderm. We could not identify the ectoderm, mesoderm, or endoderm-specific mutated genes or variants with high mutation frequency. However, there was a relatively higher mutation incidence of endoderm markers ( GATA6 ,  FOXA2 ,  GATA4 ,  AFP ) in the endoderm group, compared with the groups of ectoderm and mesoderm. Additionally, four members ( SMO, GLI1 ,  GLI2 ,  GLI3 ) within the Hedgehog signaling pathway genes showed a relatively higher mutation rate in the endoderm group than the other two groups.    Conclusions  TCGA tumors of ectoderm, mesoderm, and endoderm groups exhibit the distinct subject distribution, survival status, and genomic alteration characteristics. The synergistic mutation effect of specific genes closely related to embryonic development may contribute to the tumorigenesis of tissues or organs derived from the specific germ layers. This study provides a novel reference for exploring the functional connection between embryogenesis and tumorigenesis.

Differential genetic mutations of ectoderm, mesoderm, and endoderm-derived tumors in TCGA database