Global Medical Genetics (Jan 2024)

Expert Consensus on the Diagnosis and Treatment of <i>NRG1/2</i> Gene Fusion Solid Tumors

  • Chunwei Xu,
  • Qian Wang,
  • Dong Wang,
  • Wenxian Wang,
  • Wenfeng Fang,
  • Ziming Li,
  • Aijun Liu,
  • Jinpu Yu,
  • Wenzhao Zhong,
  • Zhijie Wang,
  • Yongchang Zhang,
  • Jingjing Liu,
  • Shirong Zhang,
  • Xiuyu Cai,
  • Anwen Liu,
  • Wen Li,
  • Ping Zhan,
  • Hongbing Liu,
  • Tangfeng Lv,
  • Liyun Miao,
  • Lingfeng Min,
  • Yu Chen,
  • Jingping Yuan,
  • Feng Wang,
  • Zhansheng Jiang,
  • Gen Lin,
  • Long Huang,
  • Xingxiang Pu,
  • Rongbo Lin,
  • Weifeng Liu,
  • Chuangzhou Rao,
  • Dongqing Lv,
  • Zongyang Yu,
  • Xiaoyan Li,
  • Chuanhao Tang,
  • Chengzhi Zhou,
  • Junping Zhang,
  • Junli Xue,
  • Hui Guo,
  • Qian Chu,
  • Rui Meng,
  • Jingxun Wu,
  • Rui Zhang,
  • Jin Zhou,
  • Zhengfei Zhu,
  • Yongheng Li,
  • Hong Qiu,
  • Fan Xia,
  • Yuanyuan Lu,
  • Xiaofeng Chen,
  • Rui Ge,
  • Enyong Dai,
  • Yu Han,
  • Weiwei Pan,
  • Fei Pang,
  • Qingqing He,
  • Jintao Huang,
  • Kai Wang,
  • Fan Wu,
  • Bingwei Xu,
  • Liping Wang,
  • Youcai Zhu,
  • Li Lin,
  • Yanru Xie,
  • Xinqing Lin,
  • Jing Cai,
  • Ling Xu,
  • Jisheng Li,
  • Xiaodong Jiao,
  • Kainan Li,
  • Jia Wei,
  • Huijing Feng,
  • Lin Wang,
  • Yingying Du,
  • Wang Yao,
  • Xuefei Shi,
  • Xiaomin Niu,
  • Dongmei Yuan,
  • Yanwen Yao,
  • Jianhui Huang,
  • Yue Feng,
  • Yinbin Zhang,
  • Pingli Sun,
  • Hong Wang,
  • Mingxiang Ye,
  • Zhaofeng Wang,
  • Yue Hao,
  • Zhen Wang,
  • Bin Wan,
  • Donglai Lv,
  • Shengjie Yang,
  • Jin Kang,
  • Jiatao Zhang,
  • Chao Zhang,
  • Juanjuan Ou,
  • Lin Shi,
  • Yina Wang,
  • Bihui Li,
  • Zhang Zhang,
  • Zhongwu Li,
  • Zhefeng Liu,
  • Nong Yang,
  • Lin Wu,
  • Huijuan Wang,
  • Gu Jin,
  • Guansong Wang,
  • Jiandong Wang,
  • Meiyu Fang,
  • Yong Fang,
  • Yuan Li,
  • Xiaojia Wang,
  • Yiping Zhang,
  • Xixu Zhu,
  • Yi Shen,
  • Shenglin Ma,
  • Biyun Wang,
  • Lu Si,
  • Yong Song,
  • Yuanzhi Lu,
  • Jing Chen,
  • Zhengbo Song

DOI
https://doi.org/10.1055/s-0044-1781457
Journal volume & issue
Vol. 11, no. 01
pp. 086 – 099

Abstract

Read online

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

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