Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

Cancer-Specific Sequences in the Diagnosis and Treatment of NUT Carcinoma: Mi-Sook Lee, Sungbin An, Ji-Young Song, Minjung Sung, Kyungsoo Jung, Eun Sol Chang, Juyoung Choi, Doo-Yi Oh, Yoon Kyung Jeon, Hobin Yang, Chaithanya Lakshmi, Sehhoon Park, Joungho Han, Se-Hoon Lee, Yoon-La Choi; Cancer Res Treat. 2023;55(2):452-467. Published online October 14, 2022; DOI: https://doi.org/10.4143/crt.2022.910

Abstract PDF Supplementary Material PubReader ePub

Purpose
NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC.
Materials and Methods
We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts.
Results
As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness.
Conclusion
This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.

Citations

Citations to this article as recorded by

Indirect targeting of MYC and direct targeting in combination with chemotherapies are more effective than direct mono-targeting in triple negative breast cancer
Negesse Mekonnen, Hobin Yang, Nirmal Rajasekaran, Kyoung Song, Yoon-La Choi, Young Kee Shin
Translational Oncology.2025; 51: 102204. CrossRef
Precision Targeting of BET Proteins - Navigating Disease Pathways, Inhibitor Insights, and Shaping Therapeutic Frontiers: A Comprehensive Review
Rakesh D. Amrutkar, Mehul V. Amesar, Lokesh B. Chavan, Nilesh S. Baviskar, Vaibhav G. Bhamare
Current Drug Targets.2025; 26(3): 147. CrossRef
NUT-midline carcinoma of the lung with rare BRD3-NUTM1 fusion
Prerana Jha, Vaishakhi Trivedi, Nandini Menon, Minit Shah, Irene A George, Rohit Mishra, Trupti Pai, Fuzail Ahmad, Venkataramanan Ramachandran, Vanita Noronha, Kumar Prabhash, Prashant Kumar
Cancer Research, Statistics, and Treatment.2024; 7(1): 110. CrossRef

6,724 View
259 Download
2 Web of Science
3 Crossref

Selection Strategies and Practical Application of BRAF V600E-Mutated Non–Small Cell Lung Carcinoma: Inwoo Hwang, Yoon-La Choi, Hyunwoo Lee, Soohyun Hwang, Boram Lee, Hobin Yang, Chaithanya Chelakkot, Joungho Han; Cancer Res Treat. 2022;54(3):782-792. Published online November 23, 2021; DOI: https://doi.org/10.4143/crt.2021.843

Abstract PDF Supplementary Material PubReader ePub

Purpose
The incidence of BRAF V600E mutation in non-small cell lung carcinoma (NSCLC) is lower than 2%, which poses difficulties in finding legitimate patients for targeted therapy. We investigated the predictive factors pertaining to BRAF V600E and the effectiveness of the VE1 antibody as a screening method for patient selection.
Materials and Methods
The study was designed into two steps. In a first group, BRAF-mutated NSCLCs were identified from sequencing data to determine the features of BRAF V600E mutation. The results of the first group helped the collection of adenocarcinomas with a papillary or micropapillary pattern but without EGFR or ALK alterations as a second group so that the frequency of BRAF V600E mutation could be calculated. The sensitivity and specificity of the VE1 were compared with BRAF V600E status.
Results
Among 39 BRAF-mutated NSCLCs in the first group, 20 (51%) were V600E. BRAF V600E mutation was more common in female patients and showed no significant correlation with smoking status. Nineteen cases were adenocarcinomas without EGFR and ALK alterations. The most common patterns of invasion were papillary and micropapillary along with central fibrosis. The sensitivity and specificity of the VE1 were 90.0% and 92.3%, respectively. In the second group, 6.7% of cases were VE1-positive, indicating that the prevalence was significantly higher than that reported in previous studies (0.3-1.8%).
Conclusion
BRAF V600E-mutated NSCLCs could be enriched with the application of clinicopathologic parameters, which are not perfect. Therefore, additional VE1 immunohistochemistry may be useful as a screening method.

Citations

Citations to this article as recorded by

High-Quality Samples for Next-Generation Sequencing and PD-L1 Assessment in Non-Small Cell Lung Cancer: The Role of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration
Marta Rodríguez González, Juan Carlos Montero González, José María Sayagués Manzano, Tamara Clavero Sánchez, Jonnathan Roldán Ruiz, Miguel Iglesias Heras, María Belén Rivas Marcos, Mar Abad Hernández, Rosa Cordovilla Pérez
Diagnostics.2025; 15(9): 1064. CrossRef
The rapidly changing field of predictive biomarkers of non-small cell lung cancer
László József Tóth, Attila Mokánszki, Gábor Méhes
Pathology and Oncology Research.2024;[Epub] CrossRef
BRAF V600E Mutation of Non-Small Cell Lung Cancer in Korean Patients
Hyo Yeong Ahn, Chang Hun Lee, Min Ki Lee, Jung Seop Eom, Yeon Joo Jeong, Yeong Dae Kim, Jeong Su Cho, Jonggeun Lee, So Jeong Lee, Dong Hoon Shin, Ahrong Kim
Medicina.2023; 59(6): 1085. CrossRef
The Impact of Liquid Biopsies Positive for EGFR Mutations on Overall Survival in Non-Small Cell Lung Cancer Patients
Jonnathan Roldan Ruiz, Marta Fuentes Gago, Luis Chinchilla Tabora, Idalia Gonzalez Morais, José Sayagués, Mar Abad Hernández, Maria Cordovilla Pérez, Maria Ludeña de la Cruz, Edel del Barco Morillo, Marta Rodriguez Gonzalez
Diagnostics.2023; 13(14): 2347. CrossRef
Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea
Sunhee Chang, Yoon-La Choi, Hyo Sup Shim, Geon Kook Lee, Seung Yeon Ha
Journal of Pathology and Translational Medicine.2022; 56(6): 334. CrossRef

6,821 View
171 Download
5 Web of Science
5 Crossref

EGFR Mutation Is Associated with Short Progression-Free Survival in Patients with Stage III Non-squamous Cell Lung Cancer Treated with Concurrent Chemoradiotherapy: Song Ee Park, Jae Myoung Noh, You Jin Kim, Han Sang Lee, Jang Ho Cho, Sung Won Lim, Yong Chan Ahn, Hongryull Pyo, Yoon-La Choi, Joungho Han, Jong-Mu Sun, Se Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn; Cancer Res Treat. 2019;51(2):493-501. Published online June 18, 2018; DOI: https://doi.org/10.4143/crt.2018.125

Abstract PDF PubReader ePub

Purpose
This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT).
Materials and Methods
From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer treated with definitive CCRT were analyzed to determine progression-free survival (PFS) and overall survival (OS) according to EGFR mutation status.
Results
Among 197 eligible patients, 81 patients were EGFR wild type, 36 patients had an EGFR mutation (exon 19 Del, n=18; L858R, n=9, uncommon [G719X, L868, T790M], n=9), and 80 patients had unknown EGFR status. The median age was 59 years (range, 28 to 80 years) and 136 patients (69.0%) were male. The median follow-up duration was 66.5 months (range, 1.9 to 114.5 months). One hundred sixty-four patients (83.2%) experienced disease progression. Median PFS was 8.9 months for the EGFR mutation group, 11.8 months for EGFR wild type, and 10.5 months for the unknown EGFR group (p=0.013 and p=0.042, respectively). The most common site of metastasis in the EGFR mutant group was the brain. However, there was no significant difference in OS among the three groups (34.6 months for EGFR mutant group vs. 31.9 months for EGFR wild type vs. 22.6 months for EGFR unknown group; p=0.792 and p=0.284). A total of 29 patients (80.6%) with EGFR mutation were treated with EGFR tyrosine kinase inhibitor (gefitinib, n=24; erlotinib, n=3; afatinib, n=2) upon progression.
Conclusion
EGFR mutation is associatedwith short PFS and the brain is the most common site of distant metastasis in patients with stage III non- squamous cell lung cancer treated with CCRT.

Citations

Citations to this article as recorded by

Economic Burden and Provider Referral Patterns Among Patients with Unresectable Stage III EGFR-Mutated NSCLC Receiving Chemoradiotherapy in the United States
YongJin Kim, Yong Zhu, Kristin J. Moore, Mary DuCharme, Dan James, Arber Shehu, Yanique Rattigan-Brown, Kim Ohaegbulam
Advances in Therapy.2025;[Epub] CrossRef
Emerging Role of Targeted Therapies Combined With Radiotherapy in Inoperable Stages I to III NSCLC: A Review From the IASLC ART Subcommittee
Sarah Bowen Jones, Clara Chan, Andrea R. Filippi, Ken Harada, Alexander V. Louie, Colin R. Lindsay, Ernest Nadal, Pablo Munoz Schuffenegger, David Woolf, Corinne Faivre-Finn
Journal of Thoracic Oncology.2025;[Epub] CrossRef
Targeted treatment for unresectable EGFR mutation-positive stage III non-small cell lung cancer: Emerging evidence and future perspectives
Terufumi Kato, Ignacio Casarini, Manuel Cobo, Corinne Faivre-Finn, Fiona Hegi-Johnson, Shun Lu, Mustafa Özgüroğlu, Suresh S. Ramalingam
Lung Cancer.2024; 187: 107414. CrossRef
Treatment patterns and survival analysis in patients with unresectable stage III EGFR-mutated non-small cell lung cancer
Huan-Wei Liang, Yang Liu, Xin-Bin Pan
Aging.2024;[Epub] CrossRef
Durvalumab after chemoradiotherapy in non‐small cell lung cancer with EGFR mutation: A real‐world study (HOT2101)
Kosuke Tsuji, Hidenori Mizugaki, Keiki Yokoo, Maki Kobayashi, Yosuke Kawashima, Nozomu Kimura, Hiroshi Yokouchi, Hajime Kikuchi, Toshiyuki Sumi, Yasutaka Kawai, Kenta Kobashi, Ryo Morita, Kenichiro Ito, Yasuo Kitamura, Hiroyuki Minemura, Keiichi Nakamura,
Cancer Science.2024; 115(4): 1273. CrossRef
Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study
Amin H. Nassar, So Yeon Kim, Jacqueline V. Aredo, Jamie Feng, Frances Shepherd, Chao Xu, David Kaldas, Jhanelle E. Gray, Thomas J. Dilling, Joel W. Neal, Heather A. Wakelee, Yufei Liu, Steven H. Lin, Tariq Abuali, Arya Amini, Yunan Nie, Tejas Patil, Anast
Journal of Thoracic Oncology.2024; 19(6): 928. CrossRef
Population Survival Kinetics Derived from Clinical Trials of Potentially Curable Lung Cancers
David J. Stewart, Katherine Cole, Dominick Bosse, Stephanie Brule, Dean Fergusson, Tim Ramsay
Current Oncology.2024; 31(3): 1600. CrossRef
Osimertinib after Chemoradiotherapy in Stage III EGFR -Mutated NSCLC
Shun Lu, Terufumi Kato, Xiaorong Dong, Myung-Ju Ahn, Le-Van Quang, Nopadol Soparattanapaisarn, Takako Inoue, Chih-Liang Wang, Meijuan Huang, James Chih-Hsin Yang, Manuel Cobo, Mustafa Özgüroğlu, Ignacio Casarini, Dang-Van Khiem, Virote Sriuranpong, Eduard
New England Journal of Medicine.2024; 391(7): 585. CrossRef
Osimertinib after definitive chemoradiotherapy in unresectable stage III epidermal growth factor receptor-mutated non-small-cell lung cancer: analyses of central nervous system efficacy and distant progression from the phase III LAURA study
S. Lu, M.-J. Ahn, T. Reungwetwattana, M. Özgüroğlu, T. Kato, J.C.-H. Yang, M. Huang, F. Fujiki, T. Inoue, L.-V. Quang, V. Sriuranpong, D. Vicente, C. Fuentes, A.A. Chaudhry, L. Poole, E. Armenteros Monterroso, Y. Rukazenkov, T. van der Gronde, S.S. Ramali
Annals of Oncology.2024; 35(12): 1116. CrossRef
Comparison of treatment regimens for unresectable stage III epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer
Xin Dai, Qian Xu, Lei Sheng, Xue Zhang, Miao Huang, Song Li, Kai Huang, Jiahui Chu, Jian Wang, Jisheng Li, Yanguo Liu, Jianyuan Zhou, Shulun Nie, Lian Liu
Chinese Medical Journal.2024;[Epub] CrossRef
Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors in patients with recurrent non-small cell lung cancer after definitive concurrent chemoradiation or radiotherapy
Jaewon Hyung, Hyunseok Yoon, Chang-Min Choi, Shinkyo Yoon, Dae Ho Lee, Sang-we Kim, Hyeong-ryul Kim, Su Ssan Kim, Si Yeol Song, Jae Cheol Lee
Journal of Cancer Research and Clinical Oncology.2023; 149(8): 4243. CrossRef
Real-world treatment patterns and clinical outcomes in EGFR-mutant locally advanced lung adenocarcinoma: A multi-center cohort study
Nan Bi, Kunpeng Xu, Hong Ge, Ming Chen, Mingyan E, Li Zhang, Jianzhong Cao, Xu Zhang, Xiao Ding, Bing Xia, Lujun Zhao, Lijie Han, Jiancheng Li, Chen Hu, Luhua Wang
Journal of the National Cancer Center.2023; 3(1): 65. CrossRef
Locally Advanced Lung Cancer
Sarah Oh, George N. Botros, Milan Patel, Missak Haigentz, Eshan Patel, Iaonnis Kontopidis, John Langenfeld, Matthew P. Deek, Salma K. Jabbour
Hematology/Oncology Clinics of North America.2023; 37(3): 533. CrossRef
Osimertinib combined with bevacizumab as the first‐line treatment in non‐small cell lung cancer patients with brain metastasis harboring epidermal growth factor receptor mutations
Ling Zhang, Yunhong You, Xueli Liu, Fengjuan Liu, Keke Nie, Youxin Ji
Thoracic Cancer.2023; 14(15): 1355. CrossRef
EGFR Mutation–Positive Unresectable Stage III Non-Squamous Lung Cancer Is Associated with a High Incidence of Brain Metastasis
Hongsik Kim, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn
Cancer Research and Treatment.2023; 55(2): 498. CrossRef
Efficacy of first-line tyrosine kinase inhibitor between unresectable stage III and stage IV EGFR-mutated non-small cell lung cancer patients
Yang Liu, Huan-Wei Liang, Xin-Bin Pan
Aging.2023;[Epub] CrossRef
Improved survival in patients with unresectable stage III EGFR‐mutant adenocarcinoma with upfront EGFR‐tyrosine kinase inhibitors
Sheng‐Yuan Wang, Ching‐Han Lai, Chian‐Wei Chen, Szu‐Chun Yang, Chao‐Chun Chang, Chia‐Ying Lin, Yi‐Ting Yen, Yau‐Lin Tseng, Po‐Lan Su, Chien‐Chung Lin, Wu‐Chou Su
Thoracic Cancer.2022; 13(2): 182. CrossRef
Nuclear accumulation of KPNA2 impacts radioresistance through positive regulation of the PLSCR1‐STAT1 loop in lung adenocarcinoma
Wei‐Chao Liao, Tsung‐Jen Lin, Yu‐Chin Liu, Yu‐Shan Wei, Guan‐Ying Chen, Hsiang‐Pu Feng, Yi‐Feng Chang, Hsin‐Tzu Chang, Chih‐Liang Wang, Hsinag‐Cheng Chi, Chun‐I Wang, Kwang‐Huei Lin, Wei‐Ting Ou Yang, Chia‐Jung Yu
Cancer Science.2022; 113(1): 205. CrossRef
An Observational Study on Treatment Outcomes in Patients With Stage III NSCLC in Taiwan: The KINDLE Study
Po-Lan Su, Gee-Chen Chang, Shih-Hsin Hsiao, Te-Chun Hsia, Meng-Chih Lin, Min-Hsi Lin, Jin-Yuan Shih, Cheng-Ta Yang, Sheng-Hsiung Yang, Yuh-Min Chen
JTO Clinical and Research Reports.2022; 3(3): 100292. CrossRef
Evaluating the Efficacy of EGFR-TKIs Combined With Radiotherapy in Advanced Lung Adenocarcinoma Patients With EGFR Mutation: A Retrospective Study
Yuxiang Wang, Wenjuan Yu, Jian Shi, Rong Qiu, Nan Jiang, Zhuofan Wang, Jie Yang, Zhongfei Jia, Meng Song
Technology in Cancer Research & Treatment.2022;[Epub] CrossRef
Durvalumab After Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer: Inferior Outcomes and Lack of Health Equity in Hispanic Patients Treated With PACIFIC Protocol (LA1-CLICaP)
Luis E. Raez, Oscar Arrieta, Diego F. Chamorro, Pamela Denisse Soberanis-Piña, Luis Corrales, Claudio Martín, Mauricio Cuello, Suraj Samtani, Gonzalo Recondo, Luis Mas, Zyanya Lucia Zatarain-Barrón, Alejandro Ruíz-Patiño, Juan Esteban García-Robledo, Cami
Frontiers in Oncology.2022;[Epub] CrossRef
The prognosis of non-small cell lung cancer patients according to endobronchial metastatic lesion
Yoonki Hong, Sunmin Park, Myoung Kyu Lee
Scientific Reports.2022;[Epub] CrossRef
First results of durvalumab after chemoradiotherapy in locally advanced non-small-cell lung cancer in Russia
D. I. Yudin, K. K. Laktionov, F. V. Moiseenko, D. M. Ponomarenko, E. A. Chekh, V. A. Chubenko, N. V. Levchenko, V. V. Kozlov, E. О. Stepanova, K. A. Sarantseva, E. S. Denisova, M. S. Ardzinba, D. Yu. Yukalchuk
Meditsinskiy sovet = Medical Council.2022; (22): 12. CrossRef
Clinical outcomes and radiation pneumonitis after concurrent EGFR‐tyrosine kinase inhibitors and radiotherapy for unresectable stage III non‐small cell lung cancer
Kunpeng Xu, Jun Liang, Tao Zhang, Zongmei Zhou, Dongfu Chen, Qinfu Feng, Zefen Xiao, Zhouguang Hui, Jima Lu, Xin Wang, Lei Deng, Wenyang Liu, Jianyang Wang, Yirui Zhai, Jie Wang, Nan Bi, Luhua Wang
Thoracic Cancer.2021; 12(6): 814. CrossRef
Durvalumab for Stage III EGFR-Mutated NSCLC After Definitive Chemoradiotherapy
Jacqueline V. Aredo, Isa Mambetsariev, Jessica A. Hellyer, Arya Amini, Joel W. Neal, Sukhmani K. Padda, Caroline E. McCoach, Jonathan W. Riess, Elwyn C. Cabebe, Jarushka Naidoo, Tariq Abuali, Ravi Salgia, Billy W. Loo, Maximilian Diehn, Summer S. Han, Hea
Journal of Thoracic Oncology.2021; 16(6): 1030. CrossRef
Einfluss der Molekularpathologie auf die onkologische Chirurgie von Leber- und Gallengangstumoren
Mazen A. Juratli, Benjamin Struecker, Shadi Katou, M. Haluk Morguel, Andreas Pascher
Der Chirurg.2021; 92(11): 1003. CrossRef
Locally Advanced, Unresectable Non-Small Cell Lung Cancer
Sonam Puri, Andreas Saltos, Bradford Perez, Xiuning Le, Jhanelle E. Gray
Current Oncology Reports.2020;[Epub] CrossRef
Real world data of durvalumab consolidation after chemoradiotherapy in stage III non-small-cell lung cancer
Hyun Ae Jung, Jae Myoung Noh, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Hongryull Pyo, Yong Chan Ahn, Keunchil Park
Lung Cancer.2020; 146: 23. CrossRef
Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small-Cell Lung Cancer (NSCLC)
Connor O’Leary, Harry Gasper, Katherine B. Sahin, Ming Tang, Arutha Kulasinghe, Mark N. Adams, Derek J. Richard, Ken J. O’Byrne
Pharmaceuticals.2020; 13(10): 273. CrossRef
MiRNAs: A New Approach to Predict and Overcome Resistance to Anticancer Drugs
Noor Altaleb
Clinical Cancer Drugs.2020; 7(2): 65. CrossRef
Incidence of brain metastasis in lung adenocarcinoma at initial diagnosis on the basis of stage and genetic alterations
Bumhee Yang, Hyun Lee, Sang-Won Um, Kyunga Kim, Jae Il Zo, Young Mog Shim, O Jung Kwon, Kyung Soo Lee, Myung-Ju Ahn, Hojoong Kim
Lung Cancer.2019; 129: 28. CrossRef
A Prediction Rule for Overall Survival in Non-Small-Cell Lung Cancer Patients with a Pathological Tumor Size Less Than 30 mm
Wang-Yu Zhu, Ke-xin Fang, Jian-ying He, Ri Cui, Yong-Kui Zhang, Han-bo Le
Disease Markers.2019; 2019: 1. CrossRef

13,525 View
475 Download
30 Web of Science
32 Crossref

Prevalence of Mutations in Discoidin Domain-Containing Receptor Tyrosine Kinase 2 (DDR2) in Squamous Cell Lung Cancers in Korean Patients: Mi-Sook Lee, Eun Ah Jung, Sung Bin An, Yu Jin Kim, Doo-Yi Oh, Ji-Young Song, Sang-Won Um, Joungho Han, Yoon-La Choi; Cancer Res Treat. 2017;49(4):1065-1076. Published online January 25, 2017; DOI: https://doi.org/10.4143/crt.2016.347

Abstract PDF Supplementary Material PubReader ePub

Purpose
The discoidin domain-containing receptor tyrosine kinase 2 (DDR2) is known to contain mutations in a small subset of patients with squamous cell carcinomas (SCC) of the lung. Studying the DDR2 mutations in patients with SCC of the lung would advance our understanding and guide the development of therapeutic strategies against lung cancer.
Materials and Methods
We selected 100 samples through a preliminary genetic screen, including specimens from biopsies and surgical resection, and confirmed SCC by histologic examination. DDR2 mutations on exons 6, 15, 16, and 18 were analyzed by Sanger sequencing of formalin-fixed, paraffin-embedded tissue samples. The functional effects of novel DDR2 mutants were confirmed by in vitro assays.
Results
We identified novel somatic mutations of DDR2 in two of the 100 SCC samples studied. One mutation was c.1745T>A (p.V582E) and the other was c.1784T>C (p.L595P), and both were on exon 15. Both patients were smokers and EGFR/KRAS/ALK-triple negative. The expression of the mutant DDR2 induced activation of DDR2 by the collagen ligand and caused enhanced cell growth and tumor progression. Moreover, dasatinib, a DDR2 inhibitor, showed potential efficacy against DDR2 L595P mutant–bearing cells.
Conclusion
Our results suggest that a mutation in DDR2 occurs naturally with a frequency of about 2% in Korean lung SCC patients. In addition, we showed that each of the novel DDR2 mutations were located in a kinase domain and induced an increase in cell proliferation rate.

Citations

Citations to this article as recorded by

Potentially functional variants of PARK7 and DDR2 in ferroptosis‐related genes predict survival of non‐small cell lung cancer patients
Huilin Wang, Hongliang Liu, Xiaozhun Tang, Guojun Lu, Sheng Luo, Mulong Du, David C. Christiani, Qingyi Wei
International Journal of Cancer.2025; 156(4): 744. CrossRef
Advances in the Treatment of Rare Mutations in Non-Small Cell Lung Cancer
Yanning Sun, Li Ma, Xiaofei Zhang, Zhaoxia Wang
OncoTargets and Therapy.2024; Volume 17: 1095. CrossRef
Discoidin Domain Receptor 2: A New Target in Cancer
Xiaoxiao Xu, Tong Yu, Zhenxing Wang
Oncology Research and Treatment.2022; 45(4): 205. CrossRef
Unearthing novel fusions as therapeutic targets in solid tumors using targeted RNA sequencing
Sungbin An, Hyun Hee Koh, Eun Sol Chang, Juyoung Choi, Ji-Young Song, Mi-Sook Lee, Yoon-La Choi
Frontiers in Oncology.2022;[Epub] CrossRef
Squamous cell lung cancer: Current landscape and future therapeutic options
Sally C.M. Lau, Yuanwang Pan, Vamsidhar Velcheti, Kwok Kin Wong
Cancer Cell.2022; 40(11): 1279. CrossRef
Complex roles of discoidin domain receptor tyrosine kinases in cancer
V. Mehta, H. Chander, A. Munshi
Clinical and Translational Oncology.2021; 23(8): 1497. CrossRef
The Yin and Yang of Discoidin Domain Receptors (DDRs): Implications in Tumor Growth and Metastasis Development
Sandra Majo, Patrick Auguste
Cancers.2021; 13(7): 1725. CrossRef
Mutational Landscape of DDR2 Gene in Lung Squamous Cell Carcinoma Using Next-generation Sequencing
Charles Ricordel, Alexandra Lespagnol, Francisco Llamas-Gutierrez, Marie de Tayrac, Mallorie Kerjouan, Alice Fievet, Houda Hamdi-Rozé, Amyrat Aliouat, Benoit Desrues, Jean Mosser, Hervé Léna
Clinical Lung Cancer.2018; 19(2): 163. CrossRef
Extracellular matrix functions in lung cancer
Martin Götte, Ilona Kovalszky
Matrix Biology.2018; 73: 105. CrossRef
Subjecting appropriate lung adenocarcinoma samples to next‐generation sequencing‐based molecular testing: challenges and possible solutions
Weihua Li, Tian Qiu, Yun Ling, Shugeng Gao, Jianming Ying
Molecular Oncology.2018; 12(5): 677. CrossRef
Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem Cells
Ugo Testa, Germana Castelli, Elvira Pelosi
Cancers.2018; 10(8): 248. CrossRef
Distribution of KRAS, DDR2, and TP53 gene mutations in lung cancer: An analysis of Iranian patients
Zahra Fathi, Seyed Ali Javad Mousavi, Raheleh Roudi, Farideh Ghazi, Sumitra Deb
PLOS ONE.2018; 13(7): e0200633. CrossRef

10,746 View
252 Download
15 Web of Science
12 Crossref

Case Report

SEC31A-ALK Fusion Gene in Lung Adenocarcinoma: Ryong Nam Kim, Yoon-La Choi, Mi-Sook Lee, Maruja E. Lira, Mao Mao, Derrick Mann, Joshua Stahl, Abel Licon, So Jung Choi, Michael Van Vrancken, Joungho Han, Iwona Wlodarska, Jhingook Kim; Cancer Res Treat. 2016;48(1):398-402. Published online February 17, 2015; DOI: https://doi.org/10.4143/crt.2014.254

Abstract PDF Supplementary Material PubReader ePub

Anaplastic lymphoma kinase (ALK) fusion is a common mechanism underlying pathogenesis of non-small cell lung carcinoma (NSCLC) where these rearrangements represent important diagnostic and therapeutic targets. In this study, we found a new ALK fusion gene, SEC31A-ALK, in lung carcinoma from a 53-year-old Korean man. The conjoined region in the fusion transcript was generated by the fusion of SEC31A exon 21 and ALK exon 20 by genomic rearrangement, which contributed to generation of an intact, in-frame open reading frame. SEC31A-ALK encodes a predicted fusion protein of 1,438 amino acids comprising the WD40 domain of SEC31A at the N-terminus and ALK kinase domain at the C-terminus. Fluorescence in situ hybridization studies suggested that SEC31A-ALK was generated by an unbalanced genomic rearrangement associated with loss of the 3′-end of SEC31A. This is the first report of SEC31A-ALK fusion transcript in clinical NSCLC, which could be a novel diagnostic and therapeutic target for patients with NSCLC.

Citations

Citations to this article as recorded by

Brigatinib treatment in a patient with advanced NSCLC with XPO1-ALK fusion: a case report
Yang Zhang, Ke-jie Li, Can Wang, Chang-lin Zou, Meng Su
Frontiers in Oncology.2025;[Epub] CrossRef
Identification of Vesicle‐Mediated Transport‐Related Genes for Predicting Prognosis, Immunotherapy Response, and Drug Screening in Cervical Cancer
Shuai Lou, Hongqing Lv, Lin Zhang
Immunity, Inflammation and Disease.2024;[Epub] CrossRef
First-line crizotinib therapy is effective for a novel SEC31A-anaplastic lymphoma kinase fusion in a patient with stage IV lung adenocarcinoma: a case report and literature reviews
Rongrong Wu, Shinan Liu, Guoli Lv, Chaowen Deng, Ruolan Wang, Shenglin Zhang, Dongyi Zhu, Le Wang, Youming Lei, Zhuang Luo
Anti-Cancer Drugs.2023; 34(2): 294. CrossRef
Hallmarks of Anaplastic Lymphoma Kinase Inhibitors with Its Quick Emergence of Drug Resistance
Yong-Fu Qiu, Lian-Hua Song, Gang-Long Jiang, Zhen Zhang, Xu-Yan Liu, Guan Wang
Pharmaceutical Fronts.2022; 04(04): e223. CrossRef
TM4SF4 and LRRK2 Are Potential Therapeutic Targets in Lung and Breast Cancers through Outlier Analysis
Kyungsoo Jung, Joon-Seok Choi, Beom-Mo Koo, Yu Jin Kim, Ji-Young Song, Minjung Sung, Eun Sol Chang, Ka-Won Noh, Sungbin An, Mi-Sook Lee, Kyoung Song, Hannah Lee, Ryong Nam Kim, Young Kee Shin, Doo-Yi Oh, Yoon-La Choi
Cancer Research and Treatment.2021; 53(1): 9. CrossRef
A case of primary pulmonary atypical carcinoid with EML4-ALK rearrangement
Na Liu, Jingjing Wang, Xiao Fu, Xiaoqiang Zheng, Huan Gao, Tao Tian, Zhiping Ruan, Yu Yao
Cancer Biology & Therapy.2020; 21(1): 12. CrossRef
Catalog of 5’ Fusion Partners in ALK-positive NSCLC Circa 2020
Sai-Hong Ignatius Ou, Viola W. Zhu, Misako Nagasaka
JTO Clinical and Research Reports.2020; 1(1): 100015. CrossRef
CircSEC31A Promotes the Malignant Progression of Non-Small Cell Lung Cancer Through Regulating SEC31A Expression via Sponging miR-376a

Fengfeng Cheng, Jing Yu, Xiaoying Zhang, Zongyan Dai, Aiju Fang
Cancer Management and Research.2020; Volume 12: 11527. CrossRef
Discovery Stories of RET Fusions in Lung Cancer: A Mini-Review
Kengo Takeuchi
Frontiers in Physiology.2019;[Epub] CrossRef
What are the Uncommon Anaplastic Lymphoma Kinase (ALK) Fusions in Non-Small Cell Lung Cancer?
Hind El Yacoubi, Mohamed Sow, Hassan Errihani
Integrative Journal of Medical Sciences.2019;[Epub] CrossRef
Crizotinib and Surgery for Long-Term Disease Control in Children and Adolescents With ALK-Positive Inflammatory Myofibroblastic Tumors
Toby Trahair, Andrew J. Gifford, Ashleigh Fordham, Chelsea Mayoh, Mitali Fadia, Robyn Lukeis, Andrew C. Wood, Santosh Valvi, Roderick D. Walker, James Blackburn, Erin E. Heyer, Tim R. Mercer, Draga Barbaric, Glenn M. Marshall, Karen L. MacKenzie
JCO Precision Oncology.2019; (3): 1. CrossRef
Perspective Insight into Future Potential Fusion Gene Transcript Biomarker Candidates in Breast Cancer
Ryong Kim, Hyeong-Gon Moon, Wonshik Han, Dong-Young Noh
International Journal of Molecular Sciences.2018; 19(2): 502. CrossRef
Integrin β3 Inhibition Enhances the Antitumor Activity of ALK Inhibitor in ALK-Rearranged NSCLC
Ka-Won Noh, Insuk Sohn, Ji-Young Song, Hyun-Tae Shin, Yu-Jin Kim, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Se-Hoon Lee, Mi-Sook Lee, Yoon-La Choi
Clinical Cancer Research.2018; 24(17): 4162. CrossRef
Combinational Analysis of FISH and Immunohistochemistry Reveals Rare Genomic Events in ALK Fusion Patterns in NSCLC that Responds to Crizotinib Treatment
Wenbin Li, Jing Zhang, Lei Guo, Shannon Chuai, Ling Shan, Jianming Ying
Journal of Thoracic Oncology.2017; 12(1): 94. CrossRef
Anchored multiplex PCR for targeted next‐generation sequencing reveals recurrent and novel USP6 fusions and upregulation of USP6 expression in aneurysmal bone cyst
Natalya V. Guseva, Omar Jaber, Munir R. Tanas, Aaron A. Stence, Ramakrishna Sompallae, Jenna Schade, Allison N. Fillman, Benjamin J. Miller, Aaron D. Bossler, Deqin Ma
Genes, Chromosomes and Cancer.2017; 56(4): 266. CrossRef
MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic Implications and Prognostic Values
Geun Dong Lee, Seung Eun Lee, Doo-Yi Oh, Dan-bi Yu, Hae Min Jeong, Jooseok Kim, Sungyoul Hong, Hun Soon Jung, Ensel Oh, Ji-Young Song, Mi-Sook Lee, Mingi Kim, Kyungsoo Jung, Jhingook Kim, Young Kee Shin, Yoon-La Choi, Hyeong Ryul Kim
Journal of Thoracic Oncology.2017; 12(8): 1233. CrossRef
Anaplastic Lymphoma Kinase Rearrangements in Non-Small-Cell Lung Cancer: Novel Applications in Diagnostics and Treatment
Rodney E Shackelford, Junaid M Ansari, Eric X Wei, Jonathan S Alexander, James Cotelingam
Pharmacogenomics.2017; 18(12): 1179. CrossRef
Molecular breakdown: a comprehensive view of anaplastic lymphoma kinase (ALK)‐rearranged non‐small cell lung cancer
Ka‐Won Noh, Mi‐Sook Lee, Seung Eun Lee, Ji‐Young Song, Hyun‐Tae Shin, Yu Jin Kim, Doo Yi Oh, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Young Mog Shim, Jae Ill Zo, Jhingook Kim, Woong‐Yang Park, Se‐Hoon Lee, Yoon‐La Choi
The Journal of Pathology.2017; 243(3): 307. CrossRef
Anaplastic large cell lymphoma: pathology, genetics, and clinical aspects
Naoko Tsuyama, Kana Sakamoto, Seiji Sakata, Akito Dobashi, Kengo Takeuchi
Journal of Clinical and Experimental Hematopathology.2017; 57(3): 120. CrossRef
Detection of ALK rearrangements in lung cancer patients using a homebrew PCR assay
Hui Yu, JianHua Chang, Fang Liu, Qifeng Wang, YongMing Lu, ZhuanXu Zhang, Jiabing Shen, Qing Zhai, Xia Meng, Jialei Wang, Xun Ye
Oncotarget.2017; 8(5): 7722. CrossRef
Worse disease-free, tumor-specific, and overall survival in surgically-resected lung adenocarcinoma patients with ALK rearrangement
Qiongqiong Gao, Pupu Li, Xiangli Jiang, Zhongli Zhan, Qingna Yan, Bo Zhang, Chun Huang
Oncotarget.2017; 8(49): 86066. CrossRef
Technological considerations for genome-guided diagnosis and management of cancer
Niall J. Lennon, Viktor A. Adalsteinsson, Stacey B. Gabriel
Genome Medicine.2016;[Epub] CrossRef
Identification of a novel partner gene, KIAA1217, fused to RET: Functional characterization and inhibitor sensitivity of two isoforms in lung adenocarcinoma
Mi-Sook Lee, Ryong Nam Kim, Hoseok I, Doo-Yi Oh, Ji-Young Song, Ka-Won Noh, Yu-Jin Kim, Jung Wook Yang, Maruja E. Lira, Chang Hun Lee, Min Ki Lee, Yeoung Dae Kim, Mao Mao, Joungho Han, Jhingook Kim, Yoon-La Choi
Oncotarget.2016; 7(24): 36101. CrossRef

15,014 View
108 Download
25 Web of Science
23 Crossref

Original Articles

Potential Role of Adjuvant Radiation Therapy in Cervical Thymic Neoplasm Involving Thyroid Gland or Neck: Jae Myoung Noh, Sang Yun Ha, Yong Chan Ahn, Dongryul Oh, Seung Won Seol, Young Lyun Oh, Joungho Han; Cancer Res Treat. 2015;47(3):436-440. Published online November 17, 2014; DOI: https://doi.org/10.4143/crt.2013.184

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to assess the clinicopathologic features, treatment outcomes, and role of adjuvant radiation therapy (RT) in cervical thymic neoplasm involving the thyroid gland or neck. Materials and Methods The medical and pathologic records of eight patients with cervical thymic neoplasm were reviewed retrospectively. All patients underwent surgical resection, including thyroidectomy or mass excision. Adjuvant RT was added in five patients with adverse clinicopathologic features. The radiation doses ranged from 54 Gy/27 fractions to 66 Gy/30 fractions delivered to the primary tumor bed and pathologically involved regional lymphatics using a 3-dimensional conformal technique. Results Eight cases of cervical thymic neoplasm included three patients with carcinoma showing thymus-like differentiation (CASTLE) and five with ectopic cervical thymoma. The histologic subtypes of ectopic cervical thymoma patients were World Health Organization (WHO) type B3 thymoma in one, WHO type B1 thymoma in two, WHO type AB thymoma in one, and metaplastic thymoma in one, respectively. The median age was 57 years (range, 40 to 76 years). Five patients received adjuvant RT: three with CASTLE; one with WHO type B3; and one with WHO type AB with local invasiveness. After a median follow-up period of 49 months (range, 11 to 203 months), no recurrence had been observed, regardless of adjuvant RT. Conclusion Adjuvant RT after surgical resection might be worthwhile in patients with CASTLE and ectopic cervical thymoma with WHO type B2-C and/or extraparenchymal extension, as similarly indicated for primary thymic epithelial tumors. A longer follow-up period may be needed in order to validate this strategy.

Citations

Citations to this article as recorded by

Coexistence of intrathyroid thymic carcinoma and papillary thyroid carcinoma: a case report and literature review
Maryam Vajihinejad, Ali Ataei, Mohammad Pashmchi, Ali Aledavoud, Vahid Zand, Mohammad Ali Broomand, Mohammad Mohammadi, Niloofar Zare Reshkuiyeh
Frontiers in Oncology.2024;[Epub] CrossRef
Case report: Thymoid differentiated carcinoma of thyroid: Two cases
Yanjie Zhao, Jiafeng Liu
Frontiers in Surgery.2023;[Epub] CrossRef
Ectopic Cervical Thymoma: An Uncommon Entity
Nikitha Kairanna, Geetha Vasudevan, Veena Karanth, Krishna Sharan
Indian Journal of Otolaryngology and Head & Neck Surgery.2022; 74(S3): 5884. CrossRef
Genomic variation associated with carcinoma showing thymus‐like elements (CASTLE) in thyroid gland
Lin Jiang, Wei‐Hui Zheng, Chao Chen
Laryngoscope Investigative Otolaryngology.2022; 7(3): 894. CrossRef
Thyroid Carcinoma Showing Thymus-like Differentiation (CASTLE): A Case Report
Mihaela Stanciu, Ruxandra Paula Ristea, Mihaela Popescu, Corina Maria Vasile, Florina Ligia Popa
Life.2022; 12(9): 1314. CrossRef
Failure pattern and suggestions for target volume delineation of carcinoma showing thymus-like differentiation treated with intensity-modulated radiotherapy
Fang-Fang Kong, Guang-Sen Pan, Rui-Ping Zhai, Cheng-Run Du, Xia-Yun He, Chun-Ying Shen, Xue-Guan Lu, Tuan-Qi Sun, Yu Wang, Qing-Hai Ji, Chao-Su Hu, Hong-Mei Ying
BMC Cancer.2022;[Epub] CrossRef
Overview of the 2022 WHO Classification of Thyroid Neoplasms
Zubair W. Baloch, Sylvia L. Asa, Justine A. Barletta, Ronald A. Ghossein, C. Christofer Juhlin, Chan Kwon Jung, Virginia A. LiVolsi, Mauro G. Papotti, Manuel Sobrinho-Simões, Giovanni Tallini, Ozgur Mete
Endocrine Pathology.2022; 33(1): 27. CrossRef
Thyroid carcinoma with thymus-like differentiation (CASTLE) tumor: а сase report
A. A. Ilyin, V. V. Polkin, P. A. Isaev, F. E. Sevrukov, N. Yu. Dvinskych, M. I. Ryzhenkova, S. A. Ivanov, A. D. Kaprin
Head and Neck Tumors (HNT).2021; 11(2): 64. CrossRef
Recurrence of carcinoma showing thymus-like differentiation (CASTLE) involving the thyroid gland
N. V. Dang, L. X. Son, N. T. T. Hong, N. T. T. Nhung, N. T. Tung, L. V. Quang
Thyroid Research.2021;[Epub] CrossRef
An extrathyroid CASTLE tumor in the left neck
Lin Jiang, Wei-hui Zheng, Yun Xi, Chao Chen
Oral Oncology.2020; 109: 104656. CrossRef
The ‘CASTLE’ tumour: An extremely rare presentation of a thyroid malignancy. A case report
Diana Mellisa Dualim, Loo Guo Hou, Shahrun Niza Abdullah Suhaimi, Nani Harlina Md Latar, Rohaizak Muhammad, Nordashima Abd Shukor
Annals of Medicine and Surgery.2019;[Epub] CrossRef
Ektopien des Thymus und ektope Thymustumoren
A. Marx, T. Rüdiger, E. Rößner, A. Tzankov, V. T. de Montpréville, R. R. Rieker, P. Ströbel, C.‑A. Weis
Der Pathologe.2018; 39(5): 390. CrossRef
CASTLE Thyroid Tumor: A Case Report and Literature Review
Chris Lominska, Christopher Fleighton Estes, Prakash C. Neupane, Y. Shnayder, Mindi J. TenNapel, Maura F. O’Neil
Frontiers in Oncology.2017;[Epub] CrossRef
Thyroid Carcinoma Showing Thymic-Like Differentiation Causing Fracture of the Trachea
Aikaterini Marini, Meletios Kanakis, Konstantinos Valakis, Nikolaos Laschos, Maria Chorti, Achilleas Lioulias
Case Reports in Medicine.2016; 2016: 1. CrossRef

12,366 View
92 Download
18 Web of Science
14 Crossref

The Relation between Histopathologic Findings on Surgical Specimen and Outcomes in Patients with N2 Positive Stage IIIA Non-Small Cell Lung Cancer Receiving Preoperative Concurrent Radiochemotherapy and Surgery: Bo Kyong Kim, Kyoung Ju Kim, Yong Chan Ahn, Do Hoon Lim, Won Park, Joungho Han, Keunchil Park, Kwan Min Kim, Jhingook Kim, Young Mog Shim; Cancer Res Treat. 2003;35(6):497-501. Published online December 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.6.497

Abstract PDF: PURPOSE
To evaluate the prognostic implication of histopathologic findings on the surgical specimens of N2 positive stage IIIA non-small cell lung cancer (NSCLC) patients who were treated with preoperative concurrent radiochemotherapy (CRCT) and surgery. MATERIALS AND METHODS: From May 1997 to April 2000, 48 patients with N2 positive stage IIIA NSCLC were treated with preoperative CRCT and surgery. Retrospective analyses were performed on 33 patients who underwent surgical resection. The thoracic radiation therapy (TRT) dose was 45 Gy over 5 weeks with a 1.8 Gy daily fraction using 10 MV X-rays. Chemotherapy consisted of two cycles of intravenous cisplatin (100 mg/m2, on days 1 and 29) and oral etoposide (50 mg/m2/day, on days 1~14 and 29~42), concurrently delivered with TRT. Surgery was performed around 4 weeks of the completion of CRCT. The median follow up was 18 months. The histopathologic findings, including the proportions of viable tumor cells, fibrosis, and necrosis, as well as the tumor and nodal statuses on the surgical specimens following the preoperative CRCT, were analyzed. RESULTS: The 3-year overall survival, disease-free survival, and local control rates were 46.1%, 49.5%, and 85.5%, respectively. Post-surgical stages decreased in 18 patients (54.5%), including 3 pathologic complete responses, were unchanged in 13 (39.4%), and increased in two (6.1%). On univariate analyses, the low proportion of the viable tumor cells was the only factor favorably affecting the overall survival rate (p=0.0386), and the histologic type of squamous cell carcinoma was a favorable factor affecting disease free survival rate (p=0.0452). On multivariate analyses, however, no factor affected the overall survival, disease free survival, or local control rates. CONCLUSION: The histopathologic findings of the proportion of viable tumor cells, fibrosis, and necrosis on the surgical specimens following preoperative CRCT had few prognostic implications on uni-and multi-variate analyses. Furthermore, the primary tumor and nodal responses to preoperative CRCT did not influence the outcomes. Longer-term follow-up with a larger number of patients, however, is awaited.

4,661 View
33 Download

First
Prev
Page of 1
Next
Last

Search