Cancer Research and Treatment

Original Articles

General

Targeted Liquid Biopsy Using Irradiation to Facilitate the Release of Cell-Free DNA from a Spatially Aimed Tumor Tissue: Jae Myoung Noh, Yeon Jeong Kim, Ho Yun Lee, Changhoon Choi, Won-Gyun Ahn, Taeseob Lee, Hongryull Pyo, Jee Hyun Park, Donghyun Park, Woong-Yang Park; Cancer Res Treat. 2022;54(1):40-53. Published online May 25, 2021; DOI: https://doi.org/10.4143/crt.2021.151

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Purpose
We investigated the feasibility of using an anatomically localized, target-enriched liquid biopsy (TLB) in mouse models of lung cancer.
Materials and Methods
After irradiating xenograft mouse with human lung cancer cell lines, H1299 (NRAS proto-oncogene, GTPase [NRAS] Q61K) and HCC827 (epidermal growth factor receptor [EGFR] E746-750del), circulating (cell-free) tumor DNA (ctDNA) levels were monitored with quantitative polymerase chain reaction on human long interspersed nuclear element-1 and cell line-specific mutations. We checked dose-dependency at 6, 12, or 18 Gy to each tumor-bearing mouse leg using 6-MV photon beams. We also analyzed ctDNA of lung cancer patients by LiquidSCAN, a targeted deep sequencing to validated the clinical performances of TLB method.
Results
Irradiation could enhance the detection sensitivity of NRAS Q61K in the plasma sample of H1299-xenograft mouse to 4.5- fold. While cell-free DNA (cfDNA) level was not changed at 6 Gy, ctDNA level was increased upon irradiation. Using double-xenograft mouse with H1299 and HCC827, ctDNA polymerase chain reaction analysis with local irradiation in each region could specify mutation type matched to transplanted cell types, proposing an anatomically localized, TLB. Furthermore, when we performed targeted deep sequencing of cfDNA to monitor ctDNA level in 11 patients with lung cancer who underwent radiotherapy, the average ctDNA level was increased within a week after the start of radiotherapy.
Conclusion
TLB using irradiation could temporarily amplify ctDNA release in xenograft mouse and lung cancer patients, which enables us to develop theragnostic method for cancer patients with accurate ctDNA detection.

Citations

Citations to this article as recorded by

Modulating cell-free DNA biology as the next frontier in liquid biopsies
Shervin Tabrizi, Carmen Martin-Alonso, Kan Xiong, Sangeeta N. Bhatia, Viktor A. Adalsteinsson, J. Christopher Love
Trends in Cell Biology.2025; 35(6): 459. CrossRef
Establishment of xenografts and methods to evaluate tumor burden for the three most frequent subclasses of pediatric-type diffuse high grade gliomas
Leire Balaguer-Lluna, Nagore G. Olaciregui, Rosario Aschero, Claudia Resa-Pares, Sonia Paco, Maria Cuadrado-Vilanova, Victor Burgueño, Merce Baulenas-Farres, Carles Monterrubio, Alejandro Manzanares, Eva Rodríguez, Cinzia Lavarino, Jaume Mora, Angel M. Ca
Journal of Neuro-Oncology.2025; 172(3): 599. CrossRef
Early Dynamics of Circulating Tumor DNA Following Curative Hypofractionated Radiotherapy Related to Disease Control in Lung Cancer
Kyungmi Yang, Jae Myoung Noh, Yeon Jeong Kim, Hongryull Pyo
Diagnostics.2025; 15(10): 1198. CrossRef
Improvement of the sensitivity of circulating tumor DNA-based liquid biopsy: current approaches and future perspectives
Ekaterina S. Kuligina, Grigoriy A. Yanus, Evgeny N. Imyanitov
Exploration of Targeted Anti-tumor Therapy.2025;[Epub] CrossRef
The VIGILANCE Study Protocol: An Innovative Study to Identify Prognostic and Response Biomarkers in Patients with Stage III Non-Small-Cell Lung Cancer Treated with Curative-Intent Radiotherapy
Ashley Horne, Amelia Payne, Harry Crawford, Clare Dempsey, Hitesh Mistry, Gareth Price, Corinne Faivre-Finn
BioMed.2025; 5(4): 27. CrossRef
Индукция выброса циркулирующей опухолевой ДНК в кровоток с помощью локального облучения опухолевого очага у пациентов с немелкоклеточным раком легкого
С.Ю. Смирнов, А.В. Медведь, А.М. Пашкевич, Ю.С. Карпейчик, С.Н. Пивоварчик, Т.Г. Вахомчик, П.Е. Короткевич, Е.И. Субоч, А.С. Портянко
Евразийский онкологический журнал.2025; 13(4): 321. CrossRef
Surpassing sensitivity limits in liquid biopsy
Tina Moser, Ellen Heitzer
Science.2024; 383(6680): 260. CrossRef
Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies
Carmen Martin-Alonso, Shervin Tabrizi, Kan Xiong, Timothy Blewett, Sainetra Sridhar, Andjela Crnjac, Sahil Patel, Zhenyi An, Ahmet Bekdemir, Douglas Shea, Shih-Ting Wang, Sergio Rodriguez-Aponte, Christopher A. Naranjo, Justin Rhoades, Jesse D. Kirkpatric
Science.2024;[Epub] CrossRef
Treatment Response Biomarkers: Working Toward Personalized Radiotherapy for Lung Cancer
Ashley Horne, Ken Harada, Katherine D. Brown, Kevin Lee Min Chua, Fiona McDonald, Gareth Price, Paul Martin Putora, Dominic G. Rothwell, Corinne Faivre-Finn
Journal of Thoracic Oncology.2024; 19(8): 1164. CrossRef
Basic Science with Preclinical Models to Investigate and Develop Liquid Biopsy: What Are the Available Data and Is It a Fruitful Approach?
Benedetta Cena, Emmanuel Melloul, Nicolas Demartines, Olivier Dormond, Ismail Labgaa
International Journal of Molecular Sciences.2022; 23(10): 5343. CrossRef
Analytical and Clinical Validation of Cell-Free Circulating Tumor DNA Assay for the Estimation of Tumor Mutational Burden
Kwang Seob Lee, Jieun Seo, Choong-Kun Lee, Saeam Shin, Zisun Choi, Seungki Min, Jun Hyuek Yang, Woo Sun Kwon, Woobin Yun, Mi Ri Park, Jong Rak Choi, Hyun Cheol Chung, Seung-Tae Lee, Sun Young Rha
Clinical Chemistry.2022; 68(12): 1519. CrossRef

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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

Revisiting diffuse gliomas in the era of precision medicine: Molecular insights and therapeutic implications
Michele Massimino, Stefania Stella, Giuseppe Di Grazia, Cristina Tomarchio, Silvia Rita Vitale, Federica Martorana, Gabriella Pellegriti, Gaetano Magro, Giuseppe Broggi, Lucia Salvatorelli, Rosario Caltabiano, Livia Manzella, Paolo Vigneri
Critical Reviews in Oncology/Hematology.2026; 227: 105511. CrossRef
Whole-Genome Sequencing Reveals a Novel GATA2 Mutation in Lower-Grade Glioma: Bioinformatics Analysis of Functional and Therapeutic Implications
Handoko, Vincent Lau, Eka Susanto, Renindra Ananda Aman, Didik Setyo Heriyanto, Soehartati A. Gondhowiardjo
Cancers.2025; 17(20): 3338. CrossRef
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
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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
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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
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Development and validation of an expanded targeted sequencing panel for non-invasive prenatal diagnosis of sporadic skeletal dysplasia
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