J Cancer 2020; 11(6):1371-1382. doi:10.7150/jca.38603

Research Paper

Practice of the New Integrated Molecular Diagnostics in Gliomas: Experiences and New Findings in a Single Chinese Center

Wan-Ming Hu1*, Fang Wang2*, Shao-Yan Xi1*, Xiao Zhang2, Jun-Peng Lai1, Hui-Yu Wu3, Li-Ling Liu1, Ke Sai4✉, Jing Zeng1✉

1. Department of Pathology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China;
2. Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center;
3. Department of General, Sun Yat-sen University Cancer Center;
4. Department of Neurosurgery, Sun Yat-sen University Cancer Center;
*These authors contributed equally to this work.

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Citation:
Hu WM, Wang F, Xi SY, Zhang X, Lai JP, Wu HY, Liu LL, Sai K, Zeng J. Practice of the New Integrated Molecular Diagnostics in Gliomas: Experiences and New Findings in a Single Chinese Center. J Cancer 2020; 11(6):1371-1382. doi:10.7150/jca.38603. Available from http://www.jcancer.org/v11p1371.htm

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Abstract

Background: The latest WHO classification of CNS tumors using the integrated phenotypic and molecular parameters (IDH, ATRX, 1p19q, TERT etc.) have reestablished the CNS tumors classification in addition to traditional histology. The establishment of glioma molecular typing can more accurately predict prognosis, better guide individualized treatment to improve survival.

Methods: The expression of IDH1, ATRX, PHH3, P53 and Ki67 was detected by IHC. Molecular status of IDH1/2 and TERT were analyzed using Sanger sequencing. MGMT was explored using methylation-specific PCR. 1p/19q codeletion status was firstly detected by FISH, then further confirmed by multiplex PCR-based next generation sequencing.

Results: The mutation frequency of IDH1 was 68.7% (79/115) in WHO II astrocytoma, and 82 cases (82/344, 23.8%) were “triple-negative glioma” in our cohort. Multivariate COX analysis revealed that only IDH, 1p/19q, TERT and MGMT were independent prognostic factors. Noteworthily, we found 7 cases of the new molecular phenotype presented as “IDH wildtype and 1p/19q codeletion”, not mentioned in the latest WHO guideline.

Conclusion: We detected the newly recommended markers in a large cohort of Chinese glioma patients. Our data demonstrated a relatively lower frequency of IDH mutations and a higher prevalence of triple-negative glioma in Chinese compared with American and European, indicating ethnic and geographical difference in some markers. In addition, the new molecular phenotype “IDH wildtype and 1p/19q codeletion” glioma deserved special focus. These findings suggest that further stratification of infiltrating gliomas is needed for different treatment strategy and precision medicine.

Keywords: IDH, ATRX, 1p/19q, TERT, MGMT, FISH, Sanger sequencing, glioma, glioblastoma