Molecular and clonal evolution in vivo reveal a common pathway of distant relapse gliomas
Guanzheng Liu,
Chaojie Bu,
Guangzhong Guo,
Zhiyue Zhang,
Zhiyuan Sheng,
Kaiyuan Deng,
Shuang Wu,
Sensen Xu,
Yage Bu,
Yushuai Gao,
Meiyun Wang,
Gang Liu,
Lingfei Kong,
Tianxiao Li,
Ming Li,
Xingyao Bu
Affiliations
Guanzheng Liu
Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Juha International Central Laboratory of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Chaojie Bu
Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Juha International Central Laboratory of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Guangzhong Guo
Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Juha International Central Laboratory of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Zhiyue Zhang
Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Juha International Central Laboratory of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Zhiyuan Sheng
Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Juha International Central Laboratory of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Kaiyuan Deng
Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Juha International Central Laboratory of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Shuang Wu
Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Juha International Central Laboratory of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Sensen Xu
Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Juha International Central Laboratory of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Yage Bu
Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Juha International Central Laboratory of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Yushuai Gao
Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Juha International Central Laboratory of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Meiyun Wang
Department of Radiology, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Gang Liu
Department of Center for Clinical Single Cell Biomedicine, Clinical Research Center, Department of Oncology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou 450003, China
Lingfei Kong
Department of Pathology, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Tianxiao Li
Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Juha International Central Laboratory of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Ming Li
Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Juha International Central Laboratory of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Corresponding author
Xingyao Bu
Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Juha International Central Laboratory of Neurosurgery, Henan Provincial People’s Hospital, Zhengzhou 450003, China; Corresponding author
Summary: The evolutionary trajectories of genomic alterations underlying distant recurrence in glioma remain largely unknown. To elucidate glioma evolution, we analyzed the evolutionary trajectories of matched pairs of primary tumors and relapse tumors or tumor in situ fluid (TISF) based on deep whole-genome sequencing data (ctDNA). We found that MMR gene mutations occurred in the late stage in IDH-mutant glioma during gene evolution, which activates multiple signaling pathways and significantly increases distant recurrence potential. The proneural subtype characterized by PDGFRA amplification was likely prone to hypermutation and distant recurrence following treatment. The classical and mesenchymal subtypes tended to progress locally through subclonal reconstruction, trunk genes transformation, and convergence evolution. EGFR and NOTCH signaling pathways and CDNK2A mutation play an important role in promoting tumor local progression. Glioma subtypes displayed distinct preferred evolutionary patterns. ClinicalTrials.gov, NCT05512325.
