- KRAS Mutation Detection in Non-small Cell Lung Cancer Using a Peptide Nucleic Acid-Mediated Polymerase Chain Reaction Clamping Method and Comparative Validation with Next-Generation Sequencing
-
Boram Lee, Boin Lee, Gangmin Han, Mi Jung Kwon, Joungho Han, Yoon-La Choi
-
Korean J Pathol. 2014;48(2):100-107. Published online April 28, 2014
-
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.100
-
-
12,556
View
-
100
Download
-
17
Crossref
-
Abstract
PDF
- Background
KRAS is one of commonly mutated genetic "drivers" in non-small cell lung cancers (NSCLCs). Recent studies indicate that patients with KRAS-mutated tumors do not benefit from adjuvant chemotherapy, so there is now a focus on targeting KRAS-mutated NSCLCs. A feasible mutation detection method is required in order to accurately test for KRAS status. MethodsWe compared direct Sanger sequencing and the peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping method in 134 NSCLCs and explored associations with clinicopathological factors. Next-generation sequencing (NGS) was used to validate the results of discordant cases. To increase the resolution of low-level somatic mutant molecules, PNA-mediated PCR clamping was used for mutant enrichment prior to NGS. ResultsTwenty-one (15.7%) cases were found to have the KRAS mutations using direct sequencing, with two additional cases by the PNA-mediated PCR clamping method. The frequencies of KRAS mutant alleles were 2% and 4%, respectively, using conventional NGS, increasing up to 90% and 89%, using mutant-enriched NGS. The KRAS mutation occurs more frequently in the tumors of smokers (p=.012) and in stage IV tumors (p=.032). ConclusionsDirect sequencing can accurately detect mutations, but, it is not always possible to obtain a tumor sample with sufficient volume. The PNA-mediated PCR clamping can rapidly provide results with sufficient sensitivity.
-
Citations
Citations to this article as recorded by 
- KRAS mutated Non‐Small Lung Carcinoma: A Real World Context from the Indian subcontinent
Ullas Batra, Shrinidhi Nathany, Mansi Sharma, Amrith BP, Joslia T. Jose, Harkirat Singh, Sakshi Mattoo, Anurag Mehta Cancer Medicine.2023; 12(3): 2869. CrossRef - Mechanism exploration and prognosis study of Astragali Radix-Spreading hedyotis herb for the treatment of lung adenocarcinoma based on bioinformatics approaches and molecular dynamics simulation
Junfeng Guo, Yuting Zhao, Xuanyu Wu, Ganggang Li, Yuwei Zhang, Yang Song, Quanyu Du Frontiers in Chemistry.2023;[Epub] CrossRef - PEAC: An Ultrasensitive and Cost-Effective MRD Detection System in Non-small Cell Lung Cancer Using Plasma Specimen
Jianping Xu, Yue Pu, Rui Lin, Shanshan Xiao, Yingxue Fu, Tao Wang Frontiers in Medicine.2022;[Epub] CrossRef - Potential applications of peptide nucleic acid in biomedical domain
Kshitij RB Singh, Parikipandla Sridevi, Ravindra Pratap Singh Engineering Reports.2020;[Epub] CrossRef - A Highly Sensitive Next-Generation Sequencing-Based Genotyping Platform for EGFR Mutations in Plasma from Non-Small Cell Lung Cancer Patients
Jung-Young Shin, Jeong-Oh Kim, Mi-Ran Lee, Seo Ree Kim, Kyongmin Sarah Beck, Jin Hyoung Kang Cancers.2020; 12(12): 3579. CrossRef - Association with PD-L1 Expression and Clinicopathological Features in 1000 Lung Cancers: A Large Single-Institution Study of Surgically Resected Lung Cancers with a High Prevalence of EGFR Mutation
Seung Eun Lee, Yu Jin Kim, Minjung Sung, Mi-Sook Lee, Joungho Han, Hong Kwan Kim, Yoon-La Choi International Journal of Molecular Sciences.2019; 20(19): 4794. CrossRef - Peptide Nucleic Acid Clamping and Direct Sequencing in the Detection of Oncogenic Alterations in Lung Cancer: Systematic Review and Meta-Analysis
Jae-Uk Song, Jonghoo Lee Yonsei Medical Journal.2018; 59(2): 211. CrossRef - Comparative analysis of Adam33 mutations in murine lung cancer cell lines by droplet digital PCR, real-time PCR and Insight Onco™ NGS
Soo-Jin Kim, Eunhee Kim, Kyung-Taek Rim Molecular & Cellular Toxicology.2018; 14(2): 221. CrossRef - KRAS mutation analysis by next‐generation sequencing in endoscopic ultrasound‐guided sampling for solid liver masses
Hyun Jong Choi, Jong Ho Moon, Hee Kyung Kim, Yun Nah Lee, Tae Hoon Lee, Sang‐Woo Cha, Young Deok Cho, Sang‐Heum Park Journal of Gastroenterology and Hepatology.2017; 32(1): 154. CrossRef - Molecular Testing of Lung Cancers
Hyo Sup Shim, Yoon-La Choi, Lucia Kim, Sunhee Chang, Wan-Seop Kim, Mee Sook Roh, Tae-Jung Kim, Seung Yeon Ha, Jin-Haeng Chung, Se Jin Jang, Geon Kook Lee Journal of Pathology and Translational Medicine.2017; 51(3): 242. CrossRef - Peptide nucleic acids: Advanced tools for biomedical applications
Anjali Gupta, Anuradha Mishra, Nidhi Puri Journal of Biotechnology.2017; 259: 148. CrossRef - Application of Peptide Nucleic Acid-based Assays Toward Detection of Somatic Mosaicism
Christopher S Hong, Chunzhang Yang, Zhengping Zhuang Molecular Therapy - Nucleic Acids.2016; 5: e314. CrossRef - Detecting Primary KIT Mutations in Presurgical Plasma of Patients with Gastrointestinal Stromal Tumor
Guhyun Kang, Byeong Seok Sohn, Jung-Soo Pyo, Jung Yeon Kim, Boram Lee, Kyoung-Mee Kim Molecular Diagnosis & Therapy.2016; 20(4): 347. CrossRef - Transformation to Small Cell Lung Cancer of Pulmonary Adenocarcinoma: Clinicopathologic Analysis of Six Cases
Soomin Ahn, Soo Hyun Hwang, Joungho Han, Yoon-La Choi, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn, Woong-Yang Park Journal of Pathology and Translational Medicine.2016; 50(4): 258. CrossRef - Clinicopathologic characteristics of EGFR, KRAS, and ALK alterations in 6,595 lung cancers
Boram Lee, Taebum Lee, Se-Hoon Lee, Yoon-La Choi, Joungho Han Oncotarget.2016; 7(17): 23874. CrossRef - Detection of KIT and PDGFRA mutations in the plasma of patients with gastrointestinal stromal tumor
Guhyun Kang, Byung Noe Bae, Byeong Seok Sohn, Jung-Soo Pyo, Gu Hyum Kang, Kyoung-Mee Kim Targeted Oncology.2015; 10(4): 597. CrossRef - Low Frequency of KRAS Mutation in Pancreatic Ductal Adenocarcinomas in Korean Patients and Its Prognostic Value
Mi Jung Kwon, Jang Yong Jeon, Hye-Rim Park, Eun Sook Nam, Seong Jin Cho, Hyung Sik Shin, Ji Hyun Kwon, Joo Seop Kim, Boram Han, Dong Hoon Kim, Yoon-La Choi Pancreas.2015; 44(3): 484. CrossRef
- Micropapillary Mucinous Adenocarcinoma of the Lung: A Brief Case Report
-
In Ho Choi, Boin Lee, Joungho Han, Chin A Yi, Yong Soo Choi, Jin Seok Ahn
-
Korean J Pathol. 2013;47(6):603-605. Published online December 24, 2013
-
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.603
-
-
7,359
View
-
44
Download
-
3
Crossref
-
PDF
-
Citations
Citations to this article as recorded by 
- Molecular Pathology of Lung Cancer
James J. Saller, Theresa A. Boyle Cold Spring Harbor Perspectives in Medicine.2022; 12(3): a037812. CrossRef - The clinicopathological significance of ALK rearrangements and KRAS and EGFR mutations in primary pulmonary mucinous adenocarcinoma
Yang Qu, Nanying Che, Dan Zhao, Chen Zhang, Dan Su, Lijuan Zhou, Lili Zhang, Chongli Wang, Haiqing Zhang, Lixin Wei Tumor Biology.2015; 36(8): 6417. CrossRef - Cytomorphological identification of advanced pulmonary adenocarcinoma harboring KRAS mutation in lymph node fine‐needle aspiration specimens: Comparative investigation of adenocarcinoma with KRAS and EGFR mutations
Dae Hyun Song, Boram Lee, Yooju Shin, In Ho Choi, Sang Yun Ha, Jae Jun Lee, Min Eui Hong, Yoon‐La Choi, Joungho Han, Sang‐Won Um Diagnostic Cytopathology.2015; 43(7): 539. CrossRef
- Cytologic Features of ALK-Positive Pulmonary Adenocarcinoma
-
Seung Yeon Ha, Jungsuk Ahn, Mee Sook Roh, Joungho Han, Jae Jun Lee, Boin Lee, Jun Yim
-
Korean J Pathol. 2013;47(3):252-257. Published online June 25, 2013
-
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.252
-
-
7,928
View
-
33
Download
-
10
Crossref
-
Abstract
PDF
- Background
The aim of this study was to determine the cytologic features of anaplastic lymphoma kinase (ALK) expressing pulmonary adenocarcinoma. MethodsWe analyzed the cytopathological
findings of 15 cases of endobronchial ultrasound guided aspiration and a case of bronchial washing. These cases were selected based on the histomorphology of ALK-rearranged lung adenocarcinoma. ResultsCytology showed mucinous (81.3%) and hemorrhagic (50%) backgrounds. The cells were arranged in tubulopapillary or tubulocribriform patterns (93.8%), and clusters (56.3%) admixed with signet ring cell features (87.5%). The tumor cells were monotonous and uniform with vesicular nuclei and a small nucleolus. ConclusionsThe characteristic findings were sheets showing a tubulopapillary or tubulocribriform appearance, with vesicular nuclei and a bland chromatin pattern (p<0.001). Scattered signet ring cells were helpful in suggesting ALK-positive adenocarcinoma (p<0.001).
-
Citations
Citations to this article as recorded by 
- Cytomorphological and histomorphological features of lung adenocarcinoma with epidermal growth factor receptor mutation and anaplastic lymphoma kinase gene rearrangement
Nikola Gardić, Aleksandra Lovrenski, Vanesa Sekeruš, Svetlana Lečić, Milorad Bijelović, Tanja Lakić, Aleksandra Ilić, Bojan Zarić, Sofija Glumac Oncology Letters.2024;[Epub] CrossRef - Machine learning‐based gene alteration prediction model for primary lung cancer using cytologic images
Shuhei Ishii, Manabu Takamatsu, Hironori Ninomiya, Kentaro Inamura, Takeshi Horai, Akira Iyoda, Naoko Honma, Rira Hoshi, Yuko Sugiyama, Noriko Yanagitani, Mingyon Mun, Hitoshi Abe, Tetuo Mikami, Kengo Takeuchi Cancer Cytopathology.2022; 130(10): 812. CrossRef - Fine‐needle aspiration cytology of non‐small cell lung carcinoma: A paradigm shift
Pranab Dey, Ratan Kumar Ghosh Diagnostic Cytopathology.2019; 47(4): 351. CrossRef - Qualitative and quantitative cytomorphological features of primary anaplastic lymphoma kinase‐positive lung cancer
Ryuko Tsukamoto, Hiroyuki Ohsaki, Sho Hosokawa, Yasunori Tokuhara, Shingo Kamoshida, Toshiko Sakuma, Tomoo Itoh, Chiho Ohbayashi Cytopathology.2019; 30(3): 295. CrossRef - Primary signet-ring adenocarcinoma of the lung: A rare lung tumor
Varun Rajpal, Rahul Kumar Sharma, Charul Dabral, Deepak Talwar South Asian Journal of Cancer.2019; 08(04): 257. CrossRef - Cytological features in eight patients with ALK‐rearranged lung cancer
Naoto Kuroda, Masahiko Ohara, Yukari Wada, Kaori Yasuoka, Keiko Mizuno, Kenji Yorita, Chiho Obayashi, Kengo Takeuchi Diagnostic Cytopathology.2018; 46(6): 516. CrossRef - Cytological markers for predicting ALK‐positive pulmonary adenocarcinoma
K. Miyata, S. Morita, H. Dejima, N. Seki, N. Matsutani, M. Mieno, F. Kondo, Y. Soejima, F. Tanaka, M. Sawabe Diagnostic Cytopathology.2017; 45(11): 963. CrossRef - ALK-rearranged adenocarcinoma with extensive mucin production can mimic mucinous adenocarcinoma: clinicopathological analysis and comprehensive histological comparison with KRAS-mutated mucinous adenocarcinoma
Yoon Jin Cha, Joungho Han, Soo Hyun Hwang, Tae Bum Lee, Hojoong Kim, Jea Ill Zo Pathology.2016; 48(4): 325. CrossRef - Cytomorphological identification of advanced pulmonary adenocarcinoma harboring KRAS mutation in lymph node fine‐needle aspiration specimens: Comparative investigation of adenocarcinoma with KRAS and EGFR mutations
Dae Hyun Song, Boram Lee, Yooju Shin, In Ho Choi, Sang Yun Ha, Jae Jun Lee, Min Eui Hong, Yoon‐La Choi, Joungho Han, Sang‐Won Um Diagnostic Cytopathology.2015; 43(7): 539. CrossRef - Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma
Seung Eun Lee, Boram Lee, Mineui Hong, Ji-Young Song, Kyungsoo Jung, Maruja E Lira, Mao Mao, Joungho Han, Jhingook Kim, Yoon-La Choi Modern Pathology.2015; 28(4): 468. CrossRef
|