Trans-Ancestry Mutation Landscape of Hepatoblastoma Genomes in Children.

Tong Li,Mingdi Ma,Liping Wang,Jie Zhao,Qian Dong,Xuemin Jian,Qian Zhang,Yuanbin Chen,Jing Zhao,Jie Liu,Zhiqiang Li,Nan Xia,Chengwen Gao,Haitao Niu,Chengzhan Zhu,Xiwei Hao

doi:10.3389/fonc.2021.669560

Abstract

Hepatoblastoma (HB) is the most common malignant tumor in the liver of infants and young children. The incidence rate varies among different populations. However, genetic differences in HB patients with different epidemiological and ancestral backgrounds have not been found. In this study, we aim to analyze data from 16 patients treated at our center and collected published data from whole-exome sequencing studies on HB, and to explore the genetic differences between races. Data from a total of 75 HB patients of three races (24 Asian, 37 Caucasian and 14 Hispanic) were analyzed. We identified 16 genes with recurrent somatic mutations and 7 core pathway modules. Among them, the Wnt/β-catenin pathway had the highest mutation rate, and the mutation frequency in Caucasians and Hispanics was approximately twice as high as that in Asians. In addition, this study compared the characteristics of gene mutations between patients who underwent preoperative chemotherapy and those who did not and found that there was no significant difference in gene mutations between the two groups. We also preliminarily verified the function of cancer-associated candidate genes (CTNNB1 and KMT2D). In conclusion, we found ethnic differences in HB biology at the genomic level, which expands our understanding of the genetics of HB in children.

Highlights

Hepatoblastoma (HB) is the most common malignant tumor in the liver of infants and young children, accounting for approximately 80% of liver tumors in children [1, 2]
To the best of our knowledge, this is the single largest Chinese population studied in this context, and it is the first time that both preoperative Chemotherapy Group (CG) and Nonchemotherapy Group (NCG) sequencing data have been included
The data from multiple ethnic groups showed that a total of 451 somatic mutations in 396 genes were detected in 75 HB patients

Summary

Introduction

Hepatoblastoma (HB) is the most common malignant tumor in the liver of infants and young children, accounting for approximately 80% of liver tumors in children [1, 2]. Studies have reported that the incidence rate of HB in Asians is higher than that in Europeans [5, 6] At present, it is not clear whether there are differences in the gene mutation landscape of HB between ancestors. Many children with HB are ineligible for resection at the initial stage of diagnosis because the tumor volume is too large or the tumor is too close to main blood vessels [7]. With the application of platinum-based neoadjuvant chemotherapy, a large number of patients who could not initially undergo surgery have achieved complete tumor resection by reducing the tumor volume before surgery, and the prognosis of children with this disease has been greatly improved [8]. Due to the lack of sequencing data from tumor samples collected after preoperative chemotherapy, no related studies have been reported

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