Cancer Research and Treatment

Review Article

Diagnostic Challenges and Clinical Implications of Microsatellite Instability/Mismatch Repair Deficiency in Solid Tumors: Yoonjin Kwak, Jeong Mo Bae, Hye Seung Lee; Cancer Res Treat. 2026;58(1):1-14. Published online December 26, 2025; DOI: https://doi.org/10.4143/crt.2025.1161

The mismatch repair (MMR) system plays a crucial role in correcting replication errors; when the MMR system is deficient (dMMR), replication errors (particularly within microsatellites) accumulate throughout the genome, leading to microsatellite instability (MSI). The key MMR genes include MLH1, MSH2, MSH6, and PMS2. Germline mutations in these genes are associated with Lynch syndrome, whereas in sporadic solid tumors, dMMR is often caused by hypermethylation of the MLH1 promoter. As the clinical use of dMMR/MSI expands, the importance of reliable testing for dMMR or MSI in companion diagnostics continues to increase. dMMR/MSI is diagnosed using immunohistochemistry (IHC) for MMR proteins, polymerase chain reaction with fragmentation analysis, or next-generation sequencing. Although IHC has technical limitations, it requires less tissue, has a short processing time, and is cost-effective. Experienced or specialized pathologists and educational efforts are helpful for reliable diagnosis, in addition to the technical aspects. Solid tumors with dMMR/MSI exhibit distinct clinicopathological features, including prognostic significance and a predictive role in adjuvant cytotoxic chemotherapy. Solid tumors with dMMR/MSI are also characterized by a higher tumor mutational burden and abundant immune cell infiltration, making them promising candidates for immune checkpoint inhibitor therapy. However, the oncogenic processes and immune microenvironment are not identical across the organs of origin, between patients, and even within the same patient, which should be considered in future studies. This review provides an overview of the practical aspects of dMMR/MSI testing, along with the molecular mechanisms and immune microenvironments associated with dMMR/MSI solid tumors.

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Evaluation of Droplet Digital PCR Assay for the Detection of Microsatellite Instability in Colorectal, Gastric, and Endometrial Cancers
Yousun Chung, Sujin Oh, Soo Kyung Nam, Hyunji Kim, Cheol Lee, Gyeong Hoon Kang, Hyeon Jeong Oh, Hye Seung Lee, Kyoung Un Park
Diagnostics.2026; 16(10): 1550. CrossRef

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Case Report

ALK Inhibition in a Patient with Inflammatory Myofibroblastic Tumor Harboring CARS1-ALK Fusion: Songji Choi, Miso Kim, Sheehyun Kim, Taekeun Park, Yoonjin Kwak, Jeong Mo Bae, Hongseok Yun, Jee Hyun Kim; Cancer Res Treat. 2025;57(3):899-904. Published online December 18, 2024; DOI: https://doi.org/10.4143/crt.2024.1184

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Inflammatory myofibroblastic tumor (IMT) is a rare entity, primarily affecting young individuals, often involving the abdomen, pelvis, or lung. Approximately 50% of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, making ALK inhibitors a viable treatment. We report a case of a 40-year-old female with metastatic IMT harboring a CARS1-ALK fusion. Initial chemotherapy failed, but targeted therapy with alectinib through the KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II study led to significant tumor regression and ongoing, durable clinical improvement of 19 months. This case highlights the importance of precision medicine and raises the reappraisal of targeted agents outside of approved indications for rare cancers with actionable genomic alterations.

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Artificial Intelligence in Lung Cancer: A Narrative Review of Recent Advances in Diagnosis, Biomarker Discovery, and Drug Development
Srikanth Basety, Renuka Gudepu, Aditya Velidandi
Pharmaceutics.2026; 18(2): 201. CrossRef
Inflammatory myofibroblastic tumors of the colon in pediatrics: clinical presentation, management, and outcomes—A case report and systematic review of literature
Ismael Elhalaby, Omar Koura, Rofyda Elhalaby, Wael Zeina, Mohamed Shareef, Essam Elhalaby
International Journal of Colorectal Disease.2025;[Epub] CrossRef
Carboplatin/etoposide/ifosfamide

Reactions Weekly.2025; 2075(1): 90. CrossRef

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Original Articles

Breast cancer

Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience: Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im; Cancer Res Treat. 2025;57(2):443-456. Published online August 21, 2024; DOI: https://doi.org/10.4143/crt.2024.296

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Purpose
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

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Comprehensive analysis of FGFR2b and its correlation with essential biomarkers, intratumoral heterogeneity, and survival in advanced gastric cancer
Yoonjin Kwak, Tae-Yong Kim, Hye Seung Lee, Soo Kyung Nam, Hyeon Jeong Oh, Do-Youn Oh, Seock-Ah Im
British Journal of Cancer.2026; 134(10): 1429. CrossRef
Genomic and transcriptomic analyses of residual invasive triple-negative breast cancer after neoadjuvant chemotherapy in the prospective MIRINAE trial (a randomized phase II trial of adjuvant atezolizumab plus capecitabine compared to capecitabine; KCSG-B
S.-A. Im, K. Park, J. Koh, C. Park, K.H. Jung, J. Lee, H.K. Ahn, A. Lee, S.H. Sim, M.H. Kim, J.H. Kim, J.H. Kim, K.E. Lee, K.H. Park, J. Bae, M.H. Lee, S. Lim, H.J. Kim, D.-W. Lee, J.H. Jeong, K.S. Lee, J. Sohn, K.J. Suh, J.-Y. Kim, Y.J. Cha, J. Moon, C.-
ESMO Open.2025; 10(10): 105804. CrossRef

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Central nervous system

Clinical and Genomic Characteristics of Adult Diffuse Midline Glioma: Changhee Park, Tae Min Kim, Jeong Mo Bae, Hongseok Yun, Jin Wook Kim, Seung Hong Choi, Soon-Tae Lee, Joo Ho Lee, Sung-Hye Park, Chul-Kee Park; Cancer Res Treat. 2021;53(2):389-398. Published online November 9, 2020; DOI: https://doi.org/10.4143/crt.2020.694

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Purpose
The treatment outcomes and genomic profiles of diffuse midline glioma (DMG) in adult patients are rarely characterized. We performed a retrospective study to evaluate the clinicogenomic profiles of adult patients with brain DMG.
Materials and Methods
Patients aged ≥ 18 years diagnosed with brain DMG at Seoul National University Hospital were included. The clinicopathological parameters, treatment outcomes, survival, and genomic profiles using 82-gene targeted next-generation sequencing (NGS) were analyzed. The 6-month progression-free survival (PFS6) after radiotherapy and overall survival (OS) were evaluated.
Results
Thirty-three patients with H3-mutant brain DMG were identified. The median OS from diagnosis was 21.8 months (95% confidence interval [CI], 13.2 to not available [NA]) and involvement of the ponto-medullary area tended to have poor OS (median OS, 20.4 months [95% CI, 9.3 to NA] vs. 43.6 months [95% CI, 18.2 to NA]; p=0.07). Twenty-four patients (72.7%) received radiotherapy with or without temozolomide. The PFS6 rate was 83.3% (n=20). Patients without progression at 6 months showed significantly prolonged OS compared with those with progression at 6 months (median OS, 24.9 months [95% CI, 20.4 to NA] vs. 10.8 months [95% CI, 4.0 to NA]; p=0.02, respectively). Targeted NGS was performed in 13 patients with DMG, among whom nine (69.2%) harbored concurrent TP53 mutation. Two patients (DMG14 and DMG23) with PIK3CA^R38S+E545K and KRAS^G12A mutations received matched therapies. Patient DMG14 received sirolimus with a PFS of 8.4 months.
Conclusion
PFS6 after radiotherapy was associated with prolonged survival in adult patients with DMG. Genome-based matched therapy may be an encouraging approach for progressive adult patients with DMG.

Citations

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Clinical, molecular characteristics, and telomere-maintaining mechanism of spinal cord glioma with or without H3 K27M mutation: a prognostic and experimental study
Haoxuan Huang, Yue Gou, Yirui Kuang, Chunbo Liu, Changwu Wu, Jun Tan
International Journal of Surgery.2026; 112(2): 2858. CrossRef
Prevalence and Clinicoradiopathological Characterization of H3 K27-Altered Diffuse Midline Gliomas in Adults—A Retrospective Observational Study
Kristof Babarczy, Bence L. Radics, Lili Kiss, Alexandra Graczer, Bence Nagy, Sandor Dosa, Gyongyi Kelemen, Marton Balazsfi, Pal Barzo, Andras Voros, Peter Klivenyi, Levente Szalardy
Pathophysiology.2026; 33(1): 21. CrossRef
Choosing Wisely between Radiotherapy Dose-Fractionation Schedules: The Molecular Graded Prognostic Assessment for Elderly Glioblastoma Patients
Hye In Lee, Jina Kim, In Ah Kim, Joo Ho Lee, Jaeho Cho, Rifaquat Rahman, Geoffrey Fell, Chan Woo Wee, Hong In Yoon
Cancer Research and Treatment.2025; 57(2): 378. CrossRef
H3F3B p.K27I-mutant diffuse midline glioma is a distinct subtype of H3K27-altered diffuse midline glioma
Lei Cheng, Min Zhou, Tao Luo, Rongfang Dong, Ni Chen, Xinyong Cai, Xingwen Wang, Hao Wu, Zan Chen, Zuowei Wang, Xueling Qi, Dehong Lu, Lianghong Teng, Fengzeng Jian, Leiming Wang
Acta Neuropathologica Communications.2025;[Epub] CrossRef
Prognostic modeling for diffuse midline glioma: development and validation of a risk stratification nomogram using SEER and institutional cohorts
Ge Zhang, Huandi Zhou, Wanyue Han, Lei Lou, Xiaoying Xue
Frontiers in Oncology.2025;[Epub] CrossRef
The role of adjuvant chemotherapy in patients with H3K27 altered diffuse midline gliomas: a multicentric retrospective study
Vincenzo Di Nunno, Giuseppe Lombardi, Matteo Simonelli, Giuseppe Minniti, Angela Mastronuzzi, Valentina Di Ruscio, Martina Corrà, Marta Padovan, Marta Maccari, Mario Caccese, Giorgia Simonetti, Arianna Berlendis, Mariangela Farinotti, Bianca Pollo, Manila
Journal of Neuro-Oncology.2024; 167(1): 145. CrossRef
Neuroradiological, genetic and clinical characteristics of histone H3 K27-mutant diffuse midline gliomas in the Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network): multicenter retrospective cohort
Nobuhide Hayashi, Junya Fukai, Hirokazu Nakatogawa, Hiroshi Kawaji, Ema Yoshioka, Yoshinori Kodama, Kosuke Nakajo, Takehiro Uda, Kentaro Naito, Noriyuki Kijima, Yoshiko Okita, Naoki Kagawa, Yoshinobu Takahashi, Naoya Hashimoto, Hideyuki Arita, Koji Takano
Acta Neuropathologica Communications.2024;[Epub] CrossRef
Genetic alteration analysis of non-pediatric diffuse midline glioma, H3 K27-altered
Hanbin Jang, Seyoung Moon, Hyun Jung Kwon, Sejoon Lee, Gheeyoung Choe, Kyu Sang Lee
Human Pathology.2024; 154: 105709. CrossRef
How to treat histone 3 altered gliomas: molecular landscape and therapeutic developments
Vincenzo Di Nunno, Enrico Franceschi, Lidia Gatto, Alicia Tosoni, Stefania Bartolini, Alba Ariela Brandes
Expert Review of Clinical Pharmacology.2023; 16(1): 17. CrossRef
Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis
Kwanghoon Lee, Seong-Ik Kim, Eric Eunshik Kim, Yu-Mi Shim, Jae-Kyung Won, Chul-Kee Park, Seung Hong Choi, Hongseok Yun, Hyunju Lee, Sung-Hye Park
Scientific Reports.2023;[Epub] CrossRef
Radiotherapy and radio‐sensitization in H3K27M‐mutated diffuse midline gliomas
Chao Liu, Shuwen Kuang, Lei Wu, Quan Cheng, Xuan Gong, Jun Wu, Longbo Zhang
CNS Neuroscience & Therapeutics.2023; 29(7): 1721. CrossRef
Volumetric response and pattern of failure of histone altered high grade glioma in adults following management with radiation therapy
A. Knight, P. Horsley, A. Yuile, J. Yim, M. Suh, V. Venketesha, M. Kastelan, H. Wheeler, M. Back
Journal of Neuro-Oncology.2023; 163(1): 281. CrossRef
Differences in survival prognosticators between children and adults with H3K27M‐mutant diffuse midline glioma
Xuan Gong, Shuwen Kuang, Dongfeng Deng, Jun Wu, Longbo Zhang, Chao Liu
CNS Neuroscience & Therapeutics.2023; 29(12): 3863. CrossRef
Adult spinal cord diffuse midline glioma, H3 K27-altered mimics symptoms of central nervous system infection: a case report
Xue Chen, Yi Li, Hui Bu, YueLi Zou, JunYing He, Hu Liu
Frontiers in Neurology.2023;[Epub] CrossRef
Clinicogenetic characteristics and the effect of radiation on the neural stem cell niche in subventricular zone-contacting glioblastoma
Jee Ye Kahng, Byung-Hee Kang, Soon-Tae Lee, Seung Hong Choi, Tae Min Kim, Chul-Kee Park, Jae-Kyung Won, Sung-Hye Park, Jaeman Son, Joo Ho Lee
Radiotherapy and Oncology.2023; 186: 109800. CrossRef
H3 K27M-Altered Diffuse Midline Gliomas: A Review
Karol Wiśniewski, Andrew Ghaly, Kate Drummond, Andreas Fahlstrӧm
Indian Journal of Neurosurgery.2023; 12(02): 104. CrossRef
Adult diffuse midline gliomas H3 K27-altered: review of a redefined entity
Carlos Axel López-Pérez, Xochitl Franco-Mojica, Ricardo Villanueva-Gaona, Alexandra Díaz-Alba, Marco Antonio Rodríguez-Florido, Victor Garcia Navarro
Journal of Neuro-Oncology.2022; 158(3): 369. CrossRef
H3K27M-Altered Diffuse Midline Gliomas Among Adult Patients: A Systematic Review of Clinical Features and Survival Analysis
Othman Bin-Alamer, Adrian E. Jimenez, Tej D. Azad, Chetan Bettegowda, Debraj Mukherjee
World Neurosurgery.2022; 165: e251. CrossRef
Molecular profile and clinical features of patients with gliomas using a broad targeted next generation‑sequencing panel
Ourania Romanidou, Paraskevi Apostolou, Kyriakos Kouvelakis, Kyriakos Tsangaras, Alexia Eliades, Achilleas Achilleos, Charalambos Loizides, Christos Lemesios, Marios Ioannides, Elena Kypri, George Koumbaris, Kyriaki Papadopoulou, Athanasios Papathanasiou,
Oncology Letters.2022;[Epub] CrossRef

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Fibroblast Growth Factor Receptor 1 (FGFR1) Amplification Detected by Droplet Digital Polymerase Chain Reaction (ddPCR) Is a Prognostic Factor in Colorectal Cancers: Jeong Mo Bae, Xianyu Wen, Tae-Shin Kim, Yoonjin Kwak, Nam-Yun Cho, Hye Seung Lee, Gyeong Hoon Kang; Cancer Res Treat. 2020;52(1):74-84. Published online May 8, 2019; DOI: https://doi.org/10.4143/crt.2019.062

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to reveal the clinicopathological characteristics and prognostic implications associated with fibroblast growth factor receptor 1 (FGFR1) amplification in colorectal cancers (CRCs).
Materials and Methods
We measured the copy number of FGFR1 by droplet digital polymerase chain reaction (ddPCR), and analyzed the FGFR1 expression by immunohistochemistry, in 764 surgically resected CRCs (SNUH2007 dataset, 384 CRCs; SNUH Folfox dataset, 380 CRCs).
Results
CRCs with ≥ 3.3 copies of the FGFR1 gene were classified as FGFR1 amplified. FGFR1 amplification was found in 10 of the 384 CRCs (2.6%) in the SNUH2007 dataset, and in 28 of the 380 CRCs (7.4%) in the SNUH Folfox dataset. In the SNUH2007 dataset, there was no association between the FGFR1 copy number status and sex, gross appearance, stage, or differentiation. High FGFR1 expression was associated with female sex and KRAS mutation. At the molecular level, FGFR1 amplification was mutually exclusive with BRAF mutation, microsatellite instability, and MLH1 methylation, in both SNUH2007 and SNUH Folfox datasets. Survival analysis revealed that FGFR1 amplification was associated with significantly worse clinical outcome compared with no FGFR1 amplification, in both SNUH2007 and SNUH Folfox datasets. Within the SNUH2007 dataset, CRC patients with high FGFR1 expression had an inferior progression-free survival compared with those with low FGFR1 expression. The FGFR inhibitor, PD173074, repressed the proliferation of a CRC cell line overexpressing FGFR1, but not of cells with FGFR1 amplification.
Conclusion
FGFR1 amplification measured by ddPCR can be a prognostic indicator of poor clinical outcome in patients with CRCs.

Citations

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Oncogenic mutations of clinical significance in colorectal cancer
Vivienne Lea, Stephanie Hui-Su Lim, Cheok Soon Lee
Pathology.2025; 57(5): 555. CrossRef
Melanin-Concentrating Hormone (MCH): Role in Mediating Reward-Motivated and Emotional Behavior and the Behavioral Disturbances Produced by Repeated Exposure to Reward Substances
Olga Karatayev, Sarah F. Leibowitz
International Journal of Molecular Sciences.2025; 26(15): 7143. CrossRef
FGFR1-amplified colorectal cancer: a distinct prognostic subtype identified through integrated genomic and immunohistochemical profiling
X. Lyu, R. Cai, B. Han, Y. Liu, Y. Zhang, Z. Wu, Y. Cheng, Z. Lin, G. Qin, X. Xie, J. Zhang, W. Zhan, Y. Deng
ESMO Open.2025; 10(9): 105561. CrossRef
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Francesco Sullo, Chiara Gallio, Laura Matteucci, Alessandro Bittoni, Margherita Muratore, Luca Esposito, Bianca Ceredi, Graziana Gallo, Paola Ulivi, Ilario Giovanni Rapposelli, Alessandro Passardi
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Di Kang, Jing Li, Jingquan Xu, Yangyang Li, Weiliang Song, Zili Zhang
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Sylvie Devalle, Veronica Aran, Cesar de Souza Bastos Júnior, Vera Lucia Pannain, Paulo Brackmann, Marcelo Leal Gregório, José Eduardo Ferreira Manso, Vivaldo Moura Neto
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Ran Zhao, Fanxiang Yin, Mangaladoss Fredimoses, Jianhua Zhao, Xiaorong Fu, Beibei Xu, Mengrui Liang, Hanyong Chen, Kangdong Liu, Mingjuan Lei, Kyle Vaughn Laster, Zhi Li, Joydeb Kumar Kundu, Zigang Dong, Mee-Hyun Lee
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César Gutiérrez Pérez, Enrique Lastra Aras, Patricia Saiz López, Enrique García Toro, Carmen Blanco Abad, Inmaculada Rodríguez Ledesma, María Pumares González, Miriam Vela Domínguez, Noelia Espinosa Cabria, Guillermo Crespo Herrero
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Heba T. Abdel‐Mohsen, Amira M. Nageeb, Iman A. Y. Ghannam
Drug Development Research.2024;[Epub] CrossRef
Clinical evaluation of a droplet digital PCR assay for detecting POLE mutations and molecular classification of endometrial cancer
Gilhyang Kim, Song Kook Lee, Dong Hoon Suh, Kidong Kim, Jae Hong No, Yong Beom Kim, Hyojin Kim
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Sergio Murolo, Marwa Moumni, Valeria Mancini, Mohamed Bechir Allagui, Lucia Landi, Gianfranco Romanazzi
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Fibroblast growth factor 2: Role in prenatal alcohol-induced stimulation of hypothalamic peptide neurons
Guo-Qing Chang, Nushrat Yasmin, Adam D. Collier, Olga Karatayev, Nailya Khalizova, Amanda Onoichenco, Milisia Fam, Avi S. Albeg, Samantha Campbell, Sarah F. Leibowitz
Progress in Neuro-Psychopharmacology and Biological Psychiatry.2022; 116: 110536. CrossRef
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Elaine S. Tan, Todd C. Knepper, Xuefeng Wang, Jennifer B. Permuth, Liang Wang, Jason B. Fleming, Hao Xie
Cancers.2022; 14(9): 2223. CrossRef
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Domenico Rendina, Veronica Abate, Giuseppe Cacace, Lanfranco D’Elia, Gianpaolo De Filippo, Silvana Del Vecchio, Ferruccio Galletti, Alberto Cuocolo, Pasquale Strazzullo
The Journal of Clinical Endocrinology & Metabolism.2022; 107(8): e3428. CrossRef
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Koshi Mimori
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Onco-ontogeny recapitulates phylogeny – a consideration
P. N. Plowman, C. E. Plowman
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Yinhao Du, Kun Fan, Xi Lu, Cen Wu
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Harriet R. Ferguson, Michael P. Smith, Chiara Francavilla
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Identification of Genomic Alterations of Perineural Invasion in Patients with Stage II Colorectal Cancer

Hao Su, Chen Chang, Jiajie Hao, Xin Xu, Mandula Bao, Shou Luo, Chuanduo Zhao, Qian Liu, Xishan Wang, Zhixiang Zhou, Haitao Zhou
OncoTargets and Therapy.2020; Volume 13: 11571. CrossRef
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