Cancer Research and Treatment

Original Articles

Clinical Targeted Next-Generation sequencing Panels for Detection of Somatic Variants in Gliomas: Hyemi Shin, Jason K. Sa, Joon Seol Bae, Harim Koo, Seonwhee Jin, Hee Jin Cho, Seung Won Choi, Jong Min Kyoung, Ja Yeon Kim, Yun Jee Seo, Je-Gun Joung, Nayoung K. D. Kim, Dae-Soon Son, Jongsuk Chung, Taeseob Lee, Doo-Sik Kong, Jung Won Choi, Ho Jun Seol, Jung-Il Lee, Yeon-Lim Suh, Woong-Yang Park, Do-Hyun Nam; Cancer Res Treat. 2020;52(1):41-50. Published online May 7, 2019; DOI: https://doi.org/10.4143/crt.2019.036

Abstract PDF Supplementary Material PubReader ePub

Purpose
Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas.
Materials and Methods
To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization.
Results
Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene.
Conclusion
We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

Citations

Citations to this article as recorded by

Comparative genomic landscape of lower-grade glioma and glioblastoma
Xinxin Sun, Qingbin Jia, Kun Li, Conghui Tian, Lili Yi, Lili Yan, Juan Zheng, Xiaodong Jia, Mingliang Gu, Michael C. Burger
PLOS ONE.2024; 19(8): e0309536. CrossRef
Actionable molecular alterations in newly diagnosed and recurrent IDH1/2 wild-type glioblastoma patients and therapeutic implications: a large mono-institutional experience using extensive next-generation sequencing analysis
Marta Padovan, Marta Maccari, Alberto Bosio, Chiara De Toni, Salvatore Vizzaccaro, Ilaria Cestonaro, Martina Corrà, Mario Caccese, Giulia Cerretti, Vittorina Zagonel, Giuseppe Lombardi
European Journal of Cancer.2023; 191: 112959. CrossRef
GPX8 regulates pan-apoptosis in gliomas to promote microglial migration and mediate immunotherapy responses
Zigui Chen, Dandan Zheng, Ziren Lin, Chunyuan Zhang, Cheng Wei, Xiandong Deng, Peng Yan, Chuanhua Zheng, Chuanliu Lan, Chengjian Qin, Xuanlei Wei, Deling Qin, Yongfang Wu, Jun Peng, Changfeng Miao, Liuxue Lu, Ying Xia, Qisheng Luo
Frontiers in Immunology.2023;[Epub] CrossRef
Comprehensive clinical assays for molecular diagnostics of gliomas: the current state and future prospects
Alina Penkova, Olga Kuziakova, Valeriia Gulaia, Vladlena Tiasto, Nikolay V. Goncharov, Daria Lanskikh, Valeriia Zhmenia, Ivan Baklanov, Vladislav Farniev, Vadim Kumeiko
Frontiers in Molecular Biosciences.2023;[Epub] CrossRef
A rapid, multiplex digital PCR assay to detect gene variants and fusions in non‐small cell lung cancer
Bryan Leatham, Katie McNall, Hari K. K. Subramanian, Lucien Jacky, John Alvarado, Dominic Yurk, Mimi Wang, Donald C. Green, Gregory J. Tsongalis, Aditya Rajagopal, Jerrod J. Schwartz
Molecular Oncology.2023; 17(11): 2221. CrossRef
Next generation sequencing in adult patients with glioblastoma in Switzerland: a multi-centre decision analysis
A. M. Zeitlberger, P. M. Putora, S. Hofer, P. Schucht, D. Migliorini, A. F. Hottinger, U. Roelcke, H. Läubli, P. Spina, O. Bozinov, M. Weller, M. C. Neidert, T. Hundsberger
Journal of Neuro-Oncology.2022; 158(3): 359. CrossRef
Targeted next‐generation sequencing of adult gliomas for retrospective prognostic evaluation and up‐front diagnostics
J. K. Petersen, H. B. Boldt, M. D. Sørensen, S. Blach, R. H. Dahlrot, S. Hansen, M. Burton, M. Thomassen, T. Kruse, F. R. Poulsen, L. Andreasen, H. Hager, B. P. Ulhøi, S. Lukacova, G. Reifenberger, B. W. Kristensen
Neuropathology and Applied Neurobiology.2021; 47(1): 108. CrossRef
Development of MR-based preoperative nomograms predicting DNA copy number subtype in lower grade gliomas with prognostic implication
Siwei Zhang, Shanshan Wu, Yun Wan, Yongsong Ye, Ying Zhang, Zelan Ma, Quanlan Guo, Hongdan Zhang, Li Xu
European Radiology.2021; 31(4): 2094. CrossRef
Comprehensive Molecular Characterization of Chinese Patients with Glioma by Extensive Next-Generation Sequencing Panel Analysis
Chun Zeng, Jing Wang, Mingwei Li, Huina Wang, Feng Lou, Shanbo Cao, Changyu Lu
Cancer Management and Research.2021; Volume 13: 3573. CrossRef
Analyzing Genetic Differences Between Sporadic Primary and Secondary/Tertiary Hyperparathyroidism by Targeted Next-Generation Panel Sequencing
Yu Ah Hong, Ki Cheol Park, Bong Kyun Kim, Jina Lee, Woo Young Sun, Hae Joung Sul, Kyung-Ah Hwang, Won Jung Choi, Yoon-Kyung Chang, Suk Young Kim, Soyoung Shin, Joonhong Park
Endocrine Pathology.2021; 32(4): 501. CrossRef
Multisite verification of the accuracy of a multi-gene next generation sequencing panel for detection of mutations and copy number alterations in solid tumours
John Bartlett, Yutaka Amemiya, Heleen Arts, Jane Bayani, Barry Eng, Daria Grafodatskaya, Suzanne Kamel Reid, Mathieu Lariviere, Bryan Lo, Rebecca McClure, Vinay Mittal, Bekim Sadikovic, Seth Sadis, Arun Seth, Jeff Smith, Xiao Zhang, Harriet Feilotter, Alv
PLOS ONE.2021; 16(10): e0258188. CrossRef
Development and validation of an expanded targeted sequencing panel for non-invasive prenatal diagnosis of sporadic skeletal dysplasia
Ching-Yuan Wang, Yen-An Tang, I-Wen Lee, Fong-Ming Chang, Chun-Wei Chien, Hsien-An Pan, H. Sunny Sun
BMC Medical Genomics.2021;[Epub] CrossRef
Therapeutic Efficacy of GC1118, a Novel Anti-EGFR Antibody, against Glioblastoma with High EGFR Amplification in Patient-Derived Xenografts
Kyoungmin Lee, Harim Koo, Yejin Kim, Donggeon Kim, Eunju Son, Heekyoung Yang, Yangmi Lim, Minkyu Hur, Hye Won Lee, Seung Won Choi, Do-Hyun Nam
Cancers.2020; 12(11): 3210. CrossRef

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Concurrent Chemoradiotherapy with Temozolomide Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients: A Retrospective Multicenter Observation Study in Korea: Byung Sup Kim, Ho Jun Seol, Do-Hyun Nam, Chul-Kee Park, Il Han Kim, Tae Min Kim, Jeong Hoon Kim, Young Hyun Cho, Sang Min Yoon, Jong Hee Chang, Seok-Gu Kang, Eui Hyun Kim, Chang-Ok Suh, Tae-Young Jung, Kyung-Hwa Lee, Chae-Yong Kim, In Ah Kim, Chang-Ki Hong, Heon Yoo, Jin Hee Kim, Shin-Hyuk Kang, Min Kyu Kang, Eun-Young Kim, Sun-Hwan Kim, Dong-Sup Chung, Sun-Chul Hwang, Joon-Ho Song, Sung Jin Cho, Sun-Il Lee, Youn-Soo Lee, Kook-Jin Ahn, Se Hoon Kim, Do Hun Lim, Ho-Shin Gwak, Se-Hoon Lee, Yong-Kil Hong; Cancer Res Treat. 2017;49(1):193-203. Published online June 27, 2016; DOI: https://doi.org/10.4143/crt.2015.473

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample.
Materials and Methods
A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively.
Results
After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients,respectively. The methylation status of O⁶-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period.
Conclusion
Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.

Citations

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Yongchao Zhang, Shichao Chen, Hualei Chen, Shanshan Chen, Zhen Li, Enshan Feng, Wei Li
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