Cancer Research and Treatment

Original Articles

Hematologic malignancy

Circulating Tumor DNA Reflects Histologic and Clinical Characteristics of Various Lymphoma Subtypes: Jin Ju Kim, Hye Min Kim, Hongkyung Kim, Soo-Jeong Kim, Seung-Tae Lee, Jong Rak Choi, Saeam Shin, Doh Yu Hwang; Cancer Res Treat. 2024;56(1):314-323. Published online July 17, 2023; DOI: https://doi.org/10.4143/crt.2023.667

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Purpose
We designed and evaluated the clinical performance of a plasma circulating tumor DNA (ctDNA) panel of 112 genes in various subtypes of lymphoma.
Materials and Methods
Targeted deep sequencing with an error-corrected algorithm was performed in ctDNA from plasma samples that were collected before treatment in 42 lymphoma patients. Blood buffy coat was utilized as a germline control. We evaluated the targeted gene panel using mutation detection concordance on the plasma samples with matched tissue samples analyzed the mutation profiles of the ctDNA.
Results
Next-generation sequencing analysis using matched tissue samples was available for 18 of the 42 patients. At least one mutation was detected in the majority of matched tissue biopsy samples (88.9%) and plasma samples (83.3%). A considerable number of mutations (40.4%) that were detected in the tissue samples were also found in the matched plasma samples. Majority of patients (21/42) were diffuse large B cell lymphoma patients. The overall detection rate of ctDNA in patients was 85.7% (36/42). The frequently mutated genes included PIM1, TET2, BCL2, KMT2D, KLHL6, HIST1H1E, and IRF8. A cutoff concentration (4,506 pg/mL) of ctDNA provided 88.9% sensitivity and 82.1% specificity to predict ctDNA mutation detection. The ctDNA concentration correlated with elevated lactate dehydrogenase level and the disease stage.
Conclusion
Our design panel can detect many actionable gene mutations, including those at low frequency. Therefore, liquid biopsy can be applied clinically in the evaluation of lymphoma patients, especially in aggressive lymphoma patients.

Citations

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Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
Blood Reviews.2024; 68: 101237. CrossRef

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Breast cancer

Implication and Influence of Multigene Panel Testing with Genetic Counseling in Korean Patients with BRCA1/2 Mutation-Negative Breast Cancer: Ji Soo Park, Saeam Shin, Yoon Jung Lee, Seung-Tae Lee, Eun Ji Nam, Jung Woo Han, Sun Hwa Lee, Tae Il Kim, Hyung Seok Park; Cancer Res Treat. 2022;54(4):1099-1110. Published online November 17, 2021; DOI: https://doi.org/10.4143/crt.2021.978

Abstract PDF Supplementary Material PubReader ePub

Purpose
The aim of the study was to evaluate the clinical implication of multigene panel testing of beyond BRCA genes in Korean patients with BRCA1/2 mutation-negative breast cancer.
Materials and Methods
Between 2016 and 2019, a total of 700 BRCA1/2 mutation-negative breast cancer patients received comprehensive multigene panel testing and genetic counseling. Among them, 347 patients completed a questionnaire about cancer worry, genetic knowledge, and preference for the method of genetic tests during pre- and post-genetic test counseling. The frequency of pathogenic and likely pathogenic variants (PV/LPV) were analyzed.
Results
At least one PV/LPV of 26 genes was found in 76 out of 700 patients (10.9 %). The rate for PV/LPV was 3.4% for high-risk genes (17 PALB2, 6 TP53, and 1 PTEN). PV/LPVs of clinical actionable genes for breast cancer management, high-risk genes and other moderate-risk genes such as ATM, BARD1, BRIP, CHEK2, NF1, and RAD51D, were observed in 7.4%. Patients who completed the questionnaire showed decreased concerns about the risk of additional cancer development (average score, 4.21 to 3.94; p < 0.001), influence on mood (3.27 to 3.13; p < 0.001), influence on daily functioning (3.03 to 2.94; p=0.006); and increased knowledge about hereditary cancer syndrome (66.9 to 68.8; p=0.025) in post-test genetic counseling. High cancer worry scales (CWSs) were associated with age ≤ 40 years and the identification of PV/LPV. Low CWSs were related to the satisfaction of the counselee.
Conclusion
Comprehensive multigene panel test with genetic counseling is clinically applicable. It should be based on interpretable genetic information, consideration of potential psychological consequences, and proper preventive strategies.

Citations

Citations to this article as recorded by

Evidence-based advancements in breast cancer genetic counseling: a review
Zahra Batool, Mohammad Amjad Kamal, Bairong Shen
Breast Cancer.2025; 32(2): 258. CrossRef
Exploring Literacy and Knowledge Gaps and Disparities in Genetics and Oncogenomics Among Cancer Patients and the General Population: A Scoping Review
Katerina Nikitara, Maria Luis Cardoso, Astrid Moura Vicente, Célia Maria Batalha Silva Rasga, Roberta De Angelis, Zeina Chamoun Morel, Arcangela De Nicolo, Maria Nomikou, Christina Karamanidou, Christine Kakalou
Healthcare.2025; 13(2): 121. CrossRef
Korean patients with hereditary cancer: a prospective multicentre cohort study protocol exploring psychosocial and health outcomes
Jun-Kyu Kim, Mi-Ae Jang, Jong Eun Park, Dongju Won, Jung-Sook Ha, Kyoung-Bo Kim, Boyoung Park, Sun-Young Kong
BMJ Open.2025; 15(2): e093905. CrossRef
PALB2 germline pathogenic variants: frequency, clinical features, and functional analysis of c.3350+5G>A variant in 3987 Korean cancer patients
M.-C. Kang, S. Lee, H. Kim, H.-S. Kang, S.-Y. Jung, J.-A. Hwang, J. Kwon, K.S. Lee, M.C. Lim, S.-Y. Park, S.H. Sim, W. Choi, J.E. Park, E.-H. Cho, S.-Y. Kong
ESMO Open.2025; 10(3): 104132. CrossRef
Human epidermal growth factor receptor-2 expression and subsequent dynamic changes in patients with ovarian cancer
Yoo-Na Kim, Yun Soo Chung, Eunhyang Park, Seung Tae Lee, Jung-Yun Lee
Scientific Reports.2024;[Epub] CrossRef
Implementation of BRCA Test among Young Breast Cancer Patients in South Korea: A Nationwide Cohort Study
Yung-Huyn Hwang, Tae-Kyung Yoo, Sae Byul Lee, Jisun Kim, Beom Seok Ko, Hee Jeong Kim, Jong Won Lee, Byung Ho Son, Il Yong Chung
Cancer Research and Treatment.2024; 56(3): 802. CrossRef
Germline RAD51C and RAD51D Mutations in High-Risk Chinese Breast and/or Ovarian Cancer Patients and Families
Ava Kwong, Cecilia Yuen Sze Ho, Chun Hang Au, Sze Keong Tey, Edmond Shiu Kwan Ma
Journal of Personalized Medicine.2024; 14(8): 866. CrossRef
Prevalence Estimation of the PALB2 Germline Variant in East Asians and Koreans through Population Database Analysis
Jong Eun Park, Min-Chae Kang, Taeheon Lee, Eun Hye Cho, Mi-Ae Jang, Dongju Won, Boyoung Park, Chang-Seok Ki, Sun-Young Kong
Cancers.2024; 16(19): 3318. CrossRef
Clinical Significance of PALB2 Pathogenic Germline Variant
Min-Chae Kang, R.N., Jong Eun Park, Mi-Ae Jang, Dongju Won, Boyoung Park, Seeyoun Lee, Dong Ock Lee, Kum Hei Ryu, Yoon-Jung Chang, Sun-Young Kong
Laboratory Medicine Online.2024; 14(4): 311. CrossRef
Clinicopathological Features and Oncological Outcomes of Germline Partner and Localizer of Breast Cancer 2-Mutated Breast Cancer in Korea
Chayanee Sae-lim, Seongyeon Jo, Shinyoung Park, Taeyong Kweon, Jeea Lee, Yoonjung Lee, Sun Hwa Lee, Dongju Won, Eun Ji Nam, Jung Woo Han, Tae Il Kim, Ji Soo Park, Hyung Seok Park
Journal of Breast Cancer.2024; 27(6): 372. CrossRef
Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer
Antonella Turchiano, Marilidia Piglionica, Stefania Martino, Rosanna Bagnulo, Antonella Garganese, Annunziata De Luisi, Stefania Chirulli, Matteo Iacoviello, Michele Stasi, Ornella Tabaku, Eleonora Meneleo, Martina Capurso, Silvia Crocetta, Simone Lattaru
Genes.2023; 14(8): 1530. CrossRef

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Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2: Kyung Jin Eoh, Ji Eun Kim, Hyung Seok Park, Seung-Tae Lee, Ji Soo Park, Jung Woo Han, Jung-Yun Lee, Sunghoon Kim, Sang Wun Kim, Jae Hoon Kim, Young Tae Kim, Eun Ji Nam; Cancer Res Treat. 2018;50(3):917-925. Published online September 27, 2017; DOI: https://doi.org/10.4143/crt.2017.220

Abstract PDF Supplementary Material PubReader ePub

Purpose
Next-generation sequencing (NGS) allows simultaneous sequencing of multiple cancer susceptibility genes and may represent a more efficient and less expensive approach than sequential testing. We assessed the frequency of germline mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene panels and NGS.
Materials and Methods
Patients with EOC (n=117) with/without a family history of breast or ovarian cancer were recruited consecutively, from March 2016 toDecember 2016.GermlineDNAwas sequenced using 35-gene NGS panel, in order to identify mutations. Upon the detection of a genetic alteration using the panel, results were cross-validated using direct sequencing.
Results
Thirty-eight patients (32.5%) had 39 pathogenic or likely pathogenic mutations in eight genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2 (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a family history of cancer, 27 (42.2%) had 27 pathogenic or likely pathogenic mutations, and six (9.3%) had mutations in genes other than BRCA1/2, such as CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0%) were identified to carry only variants of uncertain significance.
Conclusion
Using the multi-gene panel test, we found that, of all patients included in our study, 32.5% had germline cancer-predisposing mutations. NGS was confirmed to substantially improve the detection rates of a wide spectrum of mutations in EOC patients compared with those obtained with the BRCA1/2 testing alone.

Citations

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Zheng Feng, Siyu Chen, Na An, Zhihui Xiu, Xingzhu Ju, Xiaojun Chen, Rui Bi, Jie Wang, Shida Zhu, Xiaohua Wu, Hao Wen
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Siddhartha Yadav, Fergus J. Couch, Susan M. Domchek
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Germline RAD51C and RAD51D Mutations in High-Risk Chinese Breast and/or Ovarian Cancer Patients and Families
Ava Kwong, Cecilia Yuen Sze Ho, Chun Hang Au, Sze Keong Tey, Edmond Shiu Kwan Ma
Journal of Personalized Medicine.2024; 14(8): 866. CrossRef
Clinical Significance of PALB2 Pathogenic Germline Variant
Min-Chae Kang, R.N., Jong Eun Park, Mi-Ae Jang, Dongju Won, Boyoung Park, Seeyoun Lee, Dong Ock Lee, Kum Hei Ryu, Yoon-Jung Chang, Sun-Young Kong
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Tianjiao Zhao
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Dinh-Toi Chu, Mai Vu Ngoc Suong, Hue Vu Thi, Thuy-Duong Vu, Manh-Hung Nguyen, Vijai Singh
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Using species richness calculations to model the global profile of unsampled pathogenic variants: Examples from BRCA1 and BRCA2
Nandana D. Rao, Brian H. Shirts, Alvaro Galli
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Serena Bertozzi, Ambrogio Londero, Anjeza Xholli, Guglielmo Azioni, Roberta Di Vora, Michele Paudice, Ines Bucimazza, Carla Cedolini, Angelo Cagnacci
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808 Download
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Identification of a Novel BRCA1 Pathogenic Mutation in Korean Patients Following Reclassification of BRCA1 and BRCA2 Variants According to the ACMG Standards and Guidelines Using Relevant Ethnic Controls: Ji Soo Park, Eun Ji Nam, Hyung Seok Park, Jung Woo Han, Jung-Yun Lee, Jieun Kim, Tae Il Kim, Seung-Tae Lee; Cancer Res Treat. 2017;49(4):1012-1021. Published online January 17, 2017; DOI: https://doi.org/10.4143/crt.2016.433

Abstract PDF Supplementary Material PubReader ePub

Purpose
Comparison of variant frequencies in the general population has become an essential part of the American College of Medical Genetics and Genomics (ACMG) standards and guidelines for interpreting sequence variants. We determined the optimal number of relevant ethnic controls that should be used to accurately calculate the odds ratio (OR) of genetic variants.
Materials and Methods
Using the ACMG guidelines, we reclassified BRCA1 and BRCA2 mutations and variants of unknown significance in 745 Korean patients susceptible to hereditary breast and ovarian cancer compared with 1,314 Korean population controls.
Results
We observed that the ORs were falsely inflated when we analyzed several variants using non-Korean population data. Our simulation indicated that the number of controls needed for the lower limit of a 95% confidence interval to exceed 1.0 varied according to the frequency of the variant in each patient group, with more than 820 controls needed for a variant existing in 1% of cases. Using a sufficient number of relevant population data, we could efficiently classify variants and identified the BRCA1 p.Leu1780Pro mutation as a possible pathogenic founder mutation in Korean patients.
Conclusion
Our study suggests that BRCA1 p.Leu1780Pro is a novel pathogenic mutation found in Korean patients. We also determined the optimal number of relevant ethnic controls needed for accurate variant classification according to the ACMG guidelines.

Citations

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Jeong Dong Lee, Won-Ji Ryu, Hyun Ju Han, Tae Yeong Kim, Min Hwan Kim, Joohyuk Sohn
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Discovery of BRCA1/BRCA2 founder variants by haplotype analysis
Won Kyung Kwon, Hyeok-Jae Jang, Jeong Eon Lee, Yeon Hee Park, Jai Min Ryu, Jonghan Yu, Ja-Hyun Jang, Jong-Won Kim
Cancer Genetics.2022; 266-267: 19. CrossRef
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J. Tyson McDonald, Luisel J. Ricks-Santi, Alvaro Galli
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Qiting Wan, Li Hu, Tao Ouyang, Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Tie Fan, Benyao Lin, Ye Xu, Yuntao Xie
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Analysis of BRCA1/2 variants of unknown significance in the prospective Korean Hereditary Breast Cancer study
Joo Heung Kim, Sunggyun Park, Hyung Seok Park, Ji Soo Park, Seung-Tae Lee, Sung-Won Kim, Jong Won Lee, Min Hyuk Lee, Sue K. Park, Woo-Chul Noh, Doo Ho Choi, Wonshik Han, Sung Hoo Jung
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A Population-Based Analysis of BRCA1/2 Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study
Kyung-Sun Park, Woochang Lee, Moon-Woo Seong, Sun-Young Kong, Kyung-A Lee, Jung-Sook Ha, Eun-Hae Cho, Sung-Hee Han, Inho Park, Jong-Won Kim
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Colin M. E. Halverson, Laurie M. Connors, Bronson C. Wessinger, Ellen W. Clayton, Georgia L. Wiesner
Molecular Genetics & Genomic Medicine.2020;[Epub] CrossRef
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Dan Li, Yujian Shi, Ang Li, Dandan Cao, Huijun Su, Haiqi Yang, Qihuan Zhi, Yuchen Yang, Zhaoji Lan, Tianliangwen Zhou, Xiaobin You, Guifang Hu
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Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant
Hyung Seok Park, Jai Min Ryu, Ji Soo Park, Seock-Ah Im, So-Youn Jung, Eun-Kyu Kim, Woo-Chan Park, Jun Won Min, Jeeyeon Lee, Ji Young You, Jeong Eon Lee, Sung-Won Kim
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Comparison of Clinical Outcomes of BRCA1/2 Pathologic Mutation, Variants of Unknown Significance, or Wild Type Epithelial Ovarian Cancer Patients: Kyung Jin Eoh, Hyung Seok Park, Ji Soo Park, Seung-Tae Lee, Jeongwoo Han, Jung-Yun Lee, Sang Wun Kim, Sunghoon Kim, Young Tae Kim, Eun Ji Nam; Cancer Res Treat. 2017;49(2):408-415. Published online July 27, 2016; DOI: https://doi.org/10.4143/crt.2016.135

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to investigate the clinical features of epithelial ovarian cancer (EOC) patients according to BRCA1/2 mutation status (mutation, variant of uncertain significance [VUS], or wild type).
Materials and Methods
We analyzed 116 patients whose BRCA1/2 genetic test results were available for mutation type and clinical features, including progression-free survival (PFS), overall survival (OS), and response rate. These characteristics were compared according to BRCA1/2 mutation status.
Results
Thirty-seven (37/116, 31.9%) BRCA1/2 mutations were identified (BRCA1, 30; BRCA2, 7). Mutation of c.3627_3628insA (p.Leu1209_Glu1210?fs) in BRCA1 was observed in five patients (5/37, 13.5%). Twenty-five patients had BRCA1/2 VUSs (25/116, 21.6%). Personal histories of breast cancer were observed in 48.6% of patients with BRCA1/2 mutation (18/37), 16.0% of patients with BRCA1/2 VUS (4/25), and 7.4% of patients with BRCA wild type (4/54) (p < 0.001). Patients with BRCA1/2 mutation showed longer OS than those with BRCA1/2 wild type (p=0.005). No significant differences were detected in PFS, OS, or response rates between patients with BRCA1/2 VUS and BRCA1/2 mutation (p=0.772, p=0.459, and p=0.898, respectively).
Conclusion
Patientswith BRCA1/2 mutation had longer OS than thosewith BRCA1/2wild type. Patients with BRCA1/2 mutation and BRCA1/2 VUS displayed similar prognoses.

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