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

doi:10.1016/j.isci.2023.107528

Molecular and clonal evolution in vivo reveal a common pathway of distant relapse gliomas

iScience. 2023 Aug 2;26(9):107528. doi: 10.1016/j.isci.2023.107528. eCollection 2023 Sep 15.

Authors

Guanzheng Liu^{1

2}, Chaojie Bu^{1

2}, Guangzhong Guo^{1

2}, Zhiyue Zhang^{1

2}, Zhiyuan Sheng^{1

2}, Kaiyuan Deng^{1

2}, Shuang Wu^{1

2}, Sensen Xu^{1

2}, Yage Bu^{1

2}, Yushuai Gao^{1

2}, Meiyun Wang³, Gang Liu⁴, Lingfei Kong⁵, Tianxiao Li^{1

2}, Ming Li^{1

2}, Xingyao Bu^{1

2}

Affiliations

¹ Department of Neurosurgery, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou 450003, China.
² Juha International Central Laboratory of Neurosurgery, Henan Provincial People's Hospital, Zhengzhou 450003, China.
³ Department of Radiology, Henan Provincial People's Hospital, Zhengzhou 450003, China.
⁴ 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.
⁵ Department of Pathology, Henan Provincial People's Hospital, Zhengzhou 450003, China.

Abstract

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.

Keywords: Cancer; Cancer systems biology; Genomics.

Associated data

ClinicalTrials.gov/NCT05512325