Genomic profiling identified novel prognostic biomarker in Chinsese glioma patients.

Authors

null

Hainan Li

Department of Pathology, Guangdong San Jiu Brain Hospital, Guangzhou, China

Hainan Li , Changguo Shan , Chongzhu Fan , Shengnan Wu , Mingyao Lai , Linbo Cai , Dan Zhu , Fufeng Wang , Yedan Chen , Yuqian Shi , Kaihua Liu , Xian Zhang , Hua Bao , Xue Wu , Xiaonan Wang , Yang Shao , Zhi Li

Organizations

Department of Pathology, Guangdong San Jiu Brain Hospital, Guangzhou, China, Department of Neuro-oncology, Guangdong Sanjiu Brain Hospital, Guangzhou, China, Imaging Diagnosis Centre, Guangdong San Jiu Brain Hospital, Guangzhou, China, Department of Neuro-Oncology, Guangdong San Jiu Brain Hospital, Guangzhou, China, Department of Neuro-oncology, Guangdong San Jiu Brain Hospital, Guangzhou, China, Epilepsy Centre, Guangdong San Jiu Brain Hospital, Guangzhou, China, Nanjing Geneseeq Technology Inc., Nanjing, China, Translational Medicine Research Institute, Geneseeq Technology Inc., Toronto, ON, Canada, Department of Pathology, Guangdong Provincial People’s Hospital/Guangdong Academy of Medical Sciences, Guangzhou, China

Research Funding

No funding received
None

Background: Molecular charactersitcs are essential for the classification and grading of gliomas. However, majority of current understanding is based on public databases that might not accurately reflect the Asian population. Here, we studied the mutation landscape of Chinese glioma patients in hope to provide new insights for glioma prognosis and treatment. Methods: Tissue samples from 112 glioma patients underwent next-generation sequencing targeting 425 cancer-relevant genes. Gene mutations and copy number variations were investigated for their prognostic effect using overall survival data. Pathway-based survival analysis was peformed using top ten predefined oncogenic pathways. Results: We identified similar prevalence of currently established molecular diagnostic markers of glioma, including TP53 (33%), EGFR(26%), TERT (24%), PTEN (21%), ATRX (14%), BRAF (13%) and IDH1/2 (6%). Among all genetic abberations with more than 5% occurrence rate, four mutations and four copy number gains were significantly associated with poor overall survival (univariate, P < 0.05). Of these, TERT mutations (hazard ratio [HR], 3.14; 95% confidence interval [CI], 1.31 to 7.49; P = 0.01) and EGFR amplification (HR, 2.67; 95% CI, 1.20 to 5.95; P = 0.02) remained significant after adjusting for clinical parameters. Similarly, PIK3CA mutations, which was also frequently mutated in glioma but not used for clinical classification, were found to correlate with poor prognosis (HR, 2.61; 95% CI, 1.19 to 5.74; P = 0.02). Additionally, we have also identified MCL1 amplification as a potential novel biomarker for glioma (HR, 2.73; 95% CI, 1.47 to 5.07; P < 0.001), which was seldom reported in the TCGA database and might possibly be ancestral specific giving its high prevelance in our cohort (found in 32% patients). Pathway analyses revealed significantly worse prognosis with abnormal PI3K (HR, 1.81; 95% CI, 1.12 to 2.95; P = 0.02) and cell cycle pathways (HR, 2.04; 95% CI, 1.2 to 3.47; P < 0.001), both of which stayed meaningful after adjusting for clinical factors. Conclusions: In this study, we discovered PIK3CA mutations and MCL1 amplification as novel prognostic markers of glioma. We also demonstrated shorter survival with abnormal PI3K and cell cycle pathways that provided an intergrative understanding of glioma.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Publication Only

Session Title

Publication Only: Central Nervous System Tumors

Track

Central Nervous System Tumors

Sub Track

Central Nervous System Tumors

Citation

J Clin Oncol 38: 2020 (suppl; abstr e14538)

DOI

10.1200/JCO.2020.38.15_suppl.e14538

Abstract #

e14538

Abstract Disclosures

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