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

Xingjie Gao,Chunyan Zhao,Yan Zhao,Yuanyuan Ren,Chao Su,Jie Yang,Lin Ge,Nan Zhang,Xiaoteng Cui,Shaoyuan Wu,Xinxin Zhang

doi:10.1186/s12935-020-01678-x

Abstract

BackgroundIn 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.MethodsThe 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.ResultsThese 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.ConclusionsTCGA 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.

Highlights

In terms of biological behavior, gene regulation, or signaling pathways, there is a certain similarity between tumorigenesis and embryonic development of humans
For the distribution characteristics of age at diagnosis (Fig. 1d), we found that, compared with the endoderm group, the children cases account for a larger proportion in the groups of ectoderm and mesoderm
Our results suggested that a high proportion of children patients aged from 0 to 9 years old in the groups of ectoderm and mesoderm, but a high percentage of tumor cases aged 50–89 years old in the endoderm group

Summary

Introduction

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. A germ layer is a primary group of cells involved in the preliminary formation of external and internal body shape [3, 4]. The ectoderm structure eventually differentiates into the tissues or organs of the epidermis, sensory system, nervous system, gland; the mesoderm structure can form the urinary system, reproductive system, circulatory system, hematopoietic system, motor system, and connective tissue; the endoderm structure gives rise to the development of the respiratory epithelium, intestinal epithelium, digestive gland epithelium, and so on [2, 3, 5,6,7,8,9]. A variety of genetic regulatory mechanisms underlying the germ layer determination and differentiation contribute to the transformation from the initial gamete fusion to various multicellular tissues or organs of the body [8, 9, 12, 13]

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Results

Discussion

Conclusion