The Genomic Characteristics of ALK Fusion Positive Tumors in Chinese NSCLC Patients

Shaokun Liu; Tanxiao Huang; Ming Liu; Wenlong He; YingShen Zhao; Lizhen Yang; Yingjiao Long; Dandan Zong; Huihui Zeng; Yuanyuan Liu; Wenting Liao; Jingxian Duan; Subo Gong; Shifu Chen

doi:10.3389/fonc.2020.00726

The Genomic Characteristics of ALK Fusion Positive Tumors in Chinese NSCLC Patients

Front Oncol. 2020 May 8:10:726. doi: 10.3389/fonc.2020.00726. eCollection 2020.

Authors

Shaokun Liu^{1

2

3}, Tanxiao Huang⁴, Ming Liu⁴, Wenlong He^{1

2

3}, YingShen Zhao⁴, Lizhen Yang^{1

2

3}, Yingjiao Long^{1

2

3}, Dandan Zong^{1

2

3}, Huihui Zeng^{1

2

3}, Yuanyuan Liu⁴, Wenting Liao⁴, Jingxian Duan⁴, Subo Gong⁵, Shifu Chen⁴

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
² Research Unit of Respiratory Disease, Central South University, Changsha, China.
³ Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, China.
⁴ HaploX Biotechnology Co., Ltd., Shenzhen, China.
⁵ Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, China.

Abstract

Anaplastic lymphoma kinase (ALK) fusion events account for ~3-7% genetic alterations in patients with non-small cell lung cancer (NSCLC). In this study, we identified the ALK fusion patterns and a novel ALK fusion partner in 44 ALK positive NSCLC patients using a customized HapOncoCDx panel, and identified ALK fusion partners. The most common partner is EML4, forming the variant 1 (v1, E13:A20, 18/44), variant 2 (v2, E20:A20, 5/44), and variant 3 (v3, E6:A20, 13/44). Moreover, we detected a new ALK fusion partner HMBOX1. At the mutation level, TP53 is the most frequently mutated gene (24%), followed by ALK (12%) and STED2 (12%). The median tumor mutation burden (TMB) of these samples is 2.29 mutations/Mb, ranging from 0.76 mut/Mb to 16.79 muts/Mb. We further elaborately portrayed the TP53 mutation sites on the peptide sequence of the encoded protein by lollipop. The mutational signature and copy number alterations (CNAs) of the samples were also analyzed. The CNA events were found in 13 (13/44) patients, and the most commonly amplified genes were MDM2 (n = 4/13) and TERT (n = 4/13). Together, these results may guide personalized clinical management of patients with ALK fusion in the era of precision medicine.

Keywords: ALK; NGS—next generation sequencing; NSCLC; copy number aberrations; genomic landscape.