Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

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

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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.

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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

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CNS cancer

Detection of TERT Promoter Mutations Using Targeted Next-Generation Sequencing: Overcoming GC Bias through Trial and Error: Hyunwoo Lee, Boram Lee, Deok Geun Kim, Yoon Ah Cho, Jung-Sun Kim, Yeon-Lim Suh; Cancer Res Treat. 2022;54(1):75-83. Published online May 3, 2021; DOI: https://doi.org/10.4143/crt.2021.107

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Purpose
Detection of telomerase reverse transcriptase (TERT) promoter mutations is a crucial process in the integrated diagnosis of glioblastomas. However, the TERT promoter region is difficult to amplify because of its high guanine-cytosine (GC) content (> 80%). This study aimed to analyze the capturing of TERT mutations by targeted next-generation sequencing (NGS) using formalin-fixed paraffin-embedded tissues.
Materials and Methods
We compared the detection rate of TERT mutations between targeted NGS and Sanger sequencing in 25 cases of isocitrate dehydrgenase (IDH)-wildtype glioblastomas and 10 cases of non-neoplastic gastric tissues. Our customized panel consisted of 232 essential glioma-associated genes.
Results
Sanger sequencing detected TERT mutations in 17 out of 25 glioblastomas, but all TERT mutations were missed by targeted NGS. After the manual visualization of the NGS data using an integrative genomics viewer, 16 cases showed a TERT mutation with a very low read depth (mean, 21.59; median, 25), which revealed false-negative results using auto-filtering. We optimized our customized panel by extending the length of oligonucleotide baits and increasing the number of baits spanning the coverage of the TERT promoter, which did not amplify well due to the high GC content.
Conclusion
Our study confirmed that it is crucial to consider the recognition of molecular bias and to carefully interpret NGS data.

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Quality metrics for enhanced performance of an NGS panel using single-vial amplification technology
Subit Barua, Susan Hsiao, Emily Clancy, Christopher Freeman, Mahesh Mansukhani, Helen Fernandes
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Diagnostic utility of genetic alterations in distinguishing IDH‐wildtype glioblastoma from lower‐grade gliomas: Insight from next‐generation sequencing analysis of 479 cases
Boram Lee, Soohyun Hwang, Hyunsik Bae, Kyue‐Hee Choi, Yeon‐Lim Suh
Brain Pathology.2024;[Epub] CrossRef
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Ákos Kovács, Farkas Sükösd, Levente Kuthi, Imre M. Boros, Balázs Vedelek
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Oncology.2024; 102(12): 1072. CrossRef
Melanoma genomics – will we go beyond BRAF in clinics?
Justyna Mirek, Wiesław Bal, Magdalena Olbryt
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
Deep Learning Prediction of TERT Promoter Mutation Status in Thyroid Cancer Using Histologic Images
Jinhee Kim, Seokhwan Ko, Moonsik Kim, Nora Jee-Young Park, Hyungsoo Han, Junghwan Cho, Ji Young Park
Medicina.2023; 59(3): 536. CrossRef
Facilitation of Definitive Cancer Diagnosis With Quantitative Molecular Assays of BRAF V600E and TERT Promoter Variants in Patients With Thyroid Nodules
Guodong Fu, Ronald S. Chazen, Eric Monteiro, Allan Vescan, Jeremy L. Freeman, Ian J. Witterick, Christina MacMillan
JAMA Network Open.2023; 6(7): e2323500. CrossRef
Molecular Biomarkers and Recent Liquid Biopsy Testing Progress: A Review of the Application of Biosensors for the Diagnosis of Gliomas
Yuanbin Wu, Xuning Wang, Meng Zhang, Dongdong Wu
Molecules.2023; 28(15): 5660. CrossRef
Novel, clinically relevant genomic patterns identified by comprehensive genomic profiling in ATRX-deficient IDH-wildtype adult high-grade gliomas
Gábor Bedics, Péter Szőke, Bence Bátai, Tibor Nagy, Gergő Papp, Noémi Kránitz, Hajnalka Rajnai, Lilla Reiniger, Csaba Bödör, Bálint Scheich
Scientific Reports.2023;[Epub] CrossRef

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Report of the Korean Association of Lung Cancer Registry (KALC-R), 2014: Chang-Min Choi, Ho Cheol Kim, Chi Young Jung, Deog Gon Cho, Jae Hyun Jeon, Jeong Eun Lee, Jin Seok Ahn, Seung Joon Kim, Yeongdae Kim, Yoo-Duk Choi, Yang-Gun Suh, Jung-Eun Kim, Boram Lee, Young-Joo Won, Young-Chul Kim; Cancer Res Treat. 2019;51(4):1400-1410. Published online February 25, 2019; DOI: https://doi.org/10.4143/crt.2018.704

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Purpose
The aim of this study was to investigate epidemiology, clinical characteristics and sex differences of patients with lung cancer using nationwide registry in Korea.
Materials and Methods
The Korean Association for Lung Cancer developed a registry in cooperation with the Korean Central Cancer Registry, and surveyed about 10% of lung cancer cases. For this first survey of cases diagnosed in 2014, cases were selected through a systematic sampling method.
Results
Total 2,621 lung cancer patients were surveyed, and the median patient age was 70 years. During the study period, adenocarcinoma was the most frequent histologic type, the proportion of female patients was 28.4%, and women had a better prognosis (median survival, not reached vs. 13 months; p<0.001) than did men for non-small cell lung cancer. The proportion of never-smokers was 36.4%, and never-smoking was more prevalent in women than in men (87.5 vs. 16.0%, p<0.001). Epidermal growth factor receptor (EGFR) mutations were found in 36.8% of stage IV adenocarcinoma patients, and higher in female compared to male patients (51.2 vs. 26.6%, p<0.001). In addition, patients with EGFR mutation showed better survival (median survival, 18 vs. 8 months; p<0.001) than patients without EGFR mutation in these patients.
Conclusion
This is the first survey to gather unbiased nationwide lung cancer statistics in Korea. More than one-third of lung cancer patients had no smoking history. Female had a high proportion of non-smoker, more adenocarcinoma with EGFR mutation and generally better prognosis than male.

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Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients: Se-Hoon Lee, Boram Lee, Joon Ho Shim, Kwang Woo Lee, Jae Won Yun, Sook-Young Kim, Tae-You Kim, Yeul Hong Kim, Young Hyeh Ko, Hyun Cheol Chung, Chang Sik Yu, Jeeyun Lee, Sun Young Rha, Tae Won Kim, Kyung Hae Jung, Seock-Ah Im, Hyeong-Gon Moon, Sukki Cho, Jin Hyoung Kang, Jihun Kim, Sang Kyum Kim, Han Suk Ryu, Sang Yun Ha, Jong Il Kim, Yeun-Jun Chung, Cheolmin Kim, Hyung-Lae Kim, Woong-Yang Park, Dong-Young Noh, Keunchil Park; Cancer Res Treat. 2019;51(1):211-222. Published online April 23, 2018; DOI: https://doi.org/10.4143/crt.2018.132

Abstract PDF Supplementary Material PubReader ePub

Purpose
With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data.
Materials and Methods
To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared.
Results
We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration.
Conclusion
In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

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Gastroenteropancreatic Neuroendocrine Tumors with Liver Metastases in Korea: A Clinicopathological Analysis of 72 Cases in a Single Institute: Yooju Shin, Sang Yun Ha, Jiyeon Hyeon, Boram Lee, Jeeyun Lee, Kee-Taek Jang, Kyoung-Mee Kim, Young Suk Park, Cheol-Keun Park; Cancer Res Treat. 2015;47(4):738-746. Published online February 16, 2015; DOI: https://doi.org/10.4143/crt.2014.224

Abstract PDF PubReader ePub

Purpose
Management of gastroenteropancreatic (GEP) neuroendocrine tumors with liver metastases (NETLM) presents many clinical challenges. Assessment of the extent of disease and primary tumor site is crucial for management. In this study, we investigated the primary tumor sites and prognostic factors in GEP NETLM among Korean patients. Materials and Methods We reviewed the medical records of 72 Korean patients diagnosed with GEP NETLM between January 1999 and May 2013, focusing on their clinical and pathologic characteristics.
Results
The most frequently encountered primary tumor sites were the pancreas (n=25, 35%), stomach (n=8, 11%), gall bladder (n=4, 6%) and rectum (n=3, 4%). Twenty-five patients (35%) had occult primary tumor. Twelve patients (17%) had histological grade G1 tumors, 30 patients (42%) had G2 tumors, and 30 patients (42%) had G3 tumors. The mean follow-up period after histological confirmation of hepatic metastases was 11.30±2.44 months for G3 tumors, 19.67±4.09 months for G2 tumors, and 30.67±6.51 months for G1 tumors. Multivariate analyses revealed that an unknown primary tumor site (p=0.001) and higher histological grade (p < 0.001) were independent prognostic indicators for shorter overall survival (OS). Most long-term survivors (OS > 24 months) had received antitumor treatment. Conclusion The primary tumor site most frequently associated with GEP NETLM was the pancreas. Unknown primary tumor and higher histological grade were independent prognostic indicators for shorter OS. Patients identified as being at a risk of shorter OS should be followed up closely.

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