Research Paper Volume 11, Issue 23 pp 11224—11243

Genomic landscapes by multiregion sequencing combined with circulation tumor DNA detection contribute to molecular diagnosis in glioblastomas

Chao Yang1,2, , Yanli Tan3,4, , Shouwei Li5, , Junhu Zhou1,2, , Qixue Wang1,2, , Yunfei Wang1,2, , Yingbin Xie8, , Luyue Chen6, , Jie Li7, , Chuan Fang8, , Chunsheng Kang1,2,9, ,

  • 1 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
  • 2 Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Department of Neurosurgery, Tianjin Medical University General Hospital and Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China
  • 3 Department of Pathology, Affiliated Hospital of Hebei University, Baoding, China
  • 4 Department of Pathology, Hebei University Medical College, Baoding, China
  • 5 Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing, China
  • 6 Department of Neurosurgery, Zhongshan Hospital Xiamen University, Xiamen, Fujian, China
  • 7 ProteinT Biotechnologies, Co. Ltd., Tianjin, China
  • 8 Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China
  • 9 Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China

Received: September 3, 2019       Accepted: November 18, 2019       Published: December 10, 2019
How to Cite

Copyright © 2019 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Glioblastoma is a highly aggressive brain malignancy with a poor prognosis. Its high intratumor heterogeneity contributes to therapeutic resistance, tumor progression and recurrence. We sequenced 31 loci in 11 patients with glioblastoma (including one patient with samples available from the primary and recurrent tumors) to determine the genetic basis and intratumor heterogeneity of glioblastoma. By analyzing the somatic mutations, known driver genes were identified, including EGFR, PTEN and TP53, and the MUC16 gene exhibited the highest mutation rate in the samples examined. Through an evolutionary analysis of the sequencing results, the EGFR p.L861Q mutation was determined to play a role in the progression from the primary tumor to a relapsing tumor in one patient. We analyzed 1403 genes in blood-derived ctDNA that were previously revealed to play a role in tumorigenesis and the progression of cancer. Somatic mutations identified through ctDNA sequencing that match the results of multipoint exon sequencing in tumor tissues were detected, such as EGFR p.L861Q. These findings provide new insights into the intratumor heterogeneity and evolution of glioblastoma. In addition, ctDNA detection in blood samples represents a convenient method to dynamically identify the genetic changes and new therapeutic targets during the treatment of glioblastoma.


SMGs: significantly mutated genes; ctDNA: circulating tumor DNA; SNV: single-nucleotide variant; CTX: interchromosomal translocation; ITX: intrachromosomal translocation; INS: inversion; DEL: deletion; DUP: tandem duplication and INV: inversion.