Validations of Top and Novel Susceptibility Variants in All-Age Chinese Patients With Acute Lymphoblastic Leukemia

Fei Liao; Yuanxin Ye; Dandan Yin; Yun Qin; Jiangyan Zhao; Wanhua Zhang; Yan Zhang; Zhujun Deng; Yuelan Wang; Binwu Ying; Lanlan Wang; Ju Gao; Yang Shu; Yiping Zhu; Xiaoxi Lu

doi:10.3389/fgene.2020.01004

Validations of Top and Novel Susceptibility Variants in All-Age Chinese Patients With Acute Lymphoblastic Leukemia

Front Genet. 2020 Aug 25:11:1004. doi: 10.3389/fgene.2020.01004. eCollection 2020.

Authors

Fei Liao^{1

2}, Yuanxin Ye², Dandan Yin², Yun Qin³, Jiangyan Zhao², Wanhua Zhang⁴, Yan Zhang⁵, Zhujun Deng², Yuelan Wang², Binwu Ying², Lanlan Wang², Ju Gao¹, Yang Shu², Yiping Zhu¹, Xiaoxi Lu¹

Affiliations

¹ Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Pediatric Hematology/Oncology, West China Second Hospital, Sichuan University, Ministry of Education, Chengdu, China.
² State Key Laboratory of Biotherapy, Department of Laboratory Medicine, Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, China.
³ Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.
⁴ Department of Hematology and Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, China.
⁵ State Key Laboratory of Biotherapy, Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Through genome-wide association studies (GWAS), multiple inherited predispositions to acute lymphoblastic leukemia (ALL) have been identified in children. Most recently, a novel susceptibility locus at ERG was localized, exhibiting Hispanic-specific manner. In this study, we conducted a replication study to in all-age Chinese patients (N = 451), not only validating the novel ERG locus, but also systematically determining the impact of age on association status of the top GWAS signals. We found that single nucleotide polymorphisms at ARID5B, IKZF1, CEBPE, PIP4K2A were only significantly associated with ALL susceptibility in childhood patients with no BCR-ABL fusion, while GATA3 signal exhibited its significance in adults no matter carrying BCR-ABL fusion or not. Moreover, the novel ERG SNP can be validated in pediatric patients without both BCR-ABL and ETV6-RUNX1 fusion. Our finding suggests the modifying effects of age on genetic predisposition to ALL, and highlights the impact of ERG SNP in Chinese patients.

Keywords: ERG; acute lymphoblastic leukemia; all-age patients; genetic susceptibility; subtype specific.