Most Read (Last 3 years)

  • Original Article2024-03-01 Diagnostic Genetics

    Identification of Potential Genomic Alterations Using Pan-Cancer Cell-Free DNA Next-Generation Sequencing in Patients With Gastric Cancer

    Boyeon Kim , M.D., Ph.D., Yoonjung Kim , M.D., Ph.D., Jae Yong Cho , M.D., Ph.D., and Kyung-A Lee , M.D., Ph.D.

    Ann Lab Med 2024; 44(2): 164-173

    Abstract : Background: Molecular cancer profiling may lead to appropriate trials for molecularly targeted therapies. Cell-free DNA (cfDNA) is a promising diagnostic and/or prognostic biomarker in gastric cancer (GC). We characterized somatic genomic alterations in cfDNA of patients with GC. Methods: Medical records and cfDNA data of 81 patients diagnosed as having GC were reviewed. Forty-nine and 32 patients were tested using the Oncomine Pan-Cancer Cell-Free Assay on the Ion Torrent platform and AlphaLiquid 100 kit on the Illumina platform, respectively. Results: Tier I or II alterations were detected in 64.2% (52/81) of patients. Biomarkers for potential targeted therapy were detected in 55.6% of patients (45/81), and clinical trials are underway. ERBB2 amplification is actionable and was detected in 4.9% of patients (4/81). Among biomarkers showing potential for possible targeted therapy, TP53 mutation (38.3%, 35 variants in 31 patients, 31/81) and FGFR2 amplification (6.2%, 5/81) were detected the most. Conclusions: Next-generation sequencing of cfDNA is a promising technique for the molecular profiling of GC. Evidence suggests that cfDNA analysis can provide accurate and reliable information on somatic genomic alterations in patients with GC, potentially replacing tissue biopsy as a diagnostic and prognostic tool. Through cfDNA analysis for molecular profiling, it may be possible to translate the molecular classification into therapeutic targets and predictive biomarkers, leading to personalized treatment options for patients with GC in the future.

  • Original Article2023-05-01 Diagnostic Genetics

    Rapid Targeted Sequencing Using Dried Blood Spot Samples for Patients With Suspected Actionable Genetic Diseases

    Man Jin Kim , M.D., Soo Yeon Kim , M.D., Jin Sook Lee , M.D., Sanggoo Kang , M.B.A., Lae-Jeong Park , Ph.D., Wooyong Choi , B.S., Ju Yeol Jung , M.S., Taehyung Kim , M.S., Sung Sup Park , M.D., Jung Min Ko , M.D., Moon-Woo Seong , M.D., Ph.D., and Jong Hee Chae , M.D., Ph.D.

    Ann Lab Med 2023; 43(3): 280-289

    Abstract : Background: New genome sequencing technologies with enhanced diagnostic efficiency have emerged. Rapid and timely diagnosis of treatable rare genetic diseases can alter their medical management and clinical course. However, multiple factors, including ethical issues, must be considered. We designed a targeted sequencing platform to avoid ethical issues and reduce the turnaround time. Methods: We designed an automated sequencing platform using dried blood spot samples and a NEOseq_ACTION panel comprising 254 genes associated with Mendelian diseases having curable or manageable treatment options. Retrospective validation was performed using data from 24 genetically and biochemically confirmed patients. Prospective validation was performed using data from 111 patients with suspected actionable genetic diseases. Results: In prospective clinical validation, 13.5% patients presented with medically actionable diseases, including short- or medium-chain acyl-CoA dehydrogenase deficiencies (N=6), hyperphenylalaninemia (N=2), mucopolysaccharidosis type IVA (N=1), alpha thalassemia (N=1), 3-methylcrotonyl-CoA carboxylase 2 deficiency (N=1), propionic acidemia (N=1), glycogen storage disease, type IX(a) (N=1), congenital myasthenic syndrome (N=1), and citrullinemia, type II (N=1). Using the automated analytic pipeline, the turnaround time from blood collection to result reporting was

  • Letter to the Editor2023-03-01 Diagnostic Genetics

    The First Korean Case of VEXAS Syndrome Caused by a UBA1 Somatic Variant

    Jihoon G. Yoon , M.D., Ph.D., Seungbok Lee , M.D., Ph.D., Sheehyun Kim , M.D., Man Jin Kim , M.D., Ph.D., Yoon Hwan Chang , M.D., Ph.D., Jin Kyun Park , M.D., Ph.D., Dong-Yeop Shin , M.D., Ph.D., and Jangsup Moon , M.D., Ph.D.

    Ann Lab Med 2023; 43(2): 217-220
  • Guideline2024-05-01 Diagnostic Genetics

    Clinical Practice Guideline for Blood-based Circulating Tumor DNA Assays

    Jee-Soo Lee , M.D., Eun Hye Cho , M.D., Boram Kim , M.D., Jinyoung Hong , M.D., Young-gon Kim , M.D., Yoonjung Kim , M.D., Ja-Hyun Jang , M.D., Seung-Tae Lee , M.D., Sun-Young Kong , M.D., Woochang Lee , M.D., Saeam Shin , M.D., and Eun Young Song , M.D., on behalf of the Clinical Practice Guidelines Committee of the Korean Society for Laboratory Medicine

    Ann Lab Med 2024; 44(3): 195-209

    Abstract : Circulating tumor DNA (ctDNA) has emerged as a promising tool for various clinical applications, including early diagnosis, therapeutic target identification, treatment response monitoring, prognosis evaluation, and minimal residual disease detection. Consequently, ctDNA assays have been incorporated into clinical practice. In this review, we offer an in-depth exploration of the clinical implementation of ctDNA assays. Notably, we examined existing evidence related to pre-analytical procedures, analytical components in current technologies, and result interpretation and reporting processes. The primary objective of this guidelines is to provide recommendations for the clinical utilization of ctDNA assays.

  • Original Article2023-11-01 Diagnostic Genetics

    Cost-Effectiveness Analysis of Three Diagnostic Strategies for the Detection of EGFR Mutation in Advanced Non-Small Cell Lung Cancer

    Sun Mi Cho , M.D., Hye Sun Lee , Ph.D., Soyoung Jeon , Ph.D., Yoonjung Kim , M.D., Ph.D., Sun-Young Kong , M.D., Ph.D., Jin Kyung Lee , M.D., and Kyung-A Lee , M.D., Ph.D.

    Ann Lab Med 2023; 43(6): 605-613

    Abstract : Background: In non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutation testing of tumor tissue should be conducted at diagnosis. Alternatively, circulating tumor DNA can be used to detect EGFR mutation. We compared the cost and clinical effect of three strategies according to the application of the EGFR test. Methods: Decision models were developed to compare the cost-effectiveness of tissue-only, tissue-first, and plasma-first diagnostic strategies as first- and second-line treatments for NSCLC from the perspective of the Korean national healthcare payer. Progression-free survival (PFS), overall survival (OS), and direct medical costs were assessed. A one-way sensitivity analysis was performed. Results: The plasma-first strategy correctly identified numerous patients in the first- and second-line treatments. This strategy also decreased the cost of biopsy procedures and complications. Compared with that when using the other two strategies, the plasma-first strategy increased PFS by 0.5 months. The plasma-first strategy increased OS by 0.9 and 1 month compared with that when using the tissue-only and tissue-first strategies, respectively. The plasma-first strategy was the least expensive first-line treatment but the most expensive second-line treatment. First-generation tyrosine kinase inhibitor and the detection rate of the T790M mutation in tissues were the most cost-influential factors. Conclusions: The plasma-first strategy improved PFS and OS, allowing for a more accurate identification of candidates for targeted therapy for NSCLC and decreased biopsy- and complication-related costs.

  • Original Article2024-01-01 Diagnostic Genetics

    Evaluation of Group Genetic Counseling Sessions via a Metaverse-based Application

    Boeun Yoo , M.S., Arang Kim , M.S., Hye Sung Moon , M.S., Min-Kyung So , M.D., Ph.D., Tae-Dong Jeong , M.D., Ph.D., Kyoung Eun Lee , M.D., Ph.D., Byung-In Moon , M.D., Ph.D., and Jungwon Huh , M.D., Ph.D.

    Ann Lab Med 2024; 44(1): 82-91

    Abstract : Background: Group genetic counseling has been implemented to meet growing demand. A metaverse platform, in which a society is built and activities are carried out in the virtual world, has not yet been implemented in group genetic counseling. We investigated whether a metaverse platform could be an alternative service-delivery model for group genetic counseling. Methods: Participants (N=131) were divided into three groups: patient (N=45), family (N= 43), and interested (N=43) groups. Participants entered the metaverse through a link sent to their mobile phones and attended a 20-min group genetic counseling session reviewing hereditary breast cancer, followed by a 10-min question-and-answer period. Results: The overall median score of post-educational knowledge (9.0, range 8.0–10.0) significantly increased compared to that of pre-educational knowledge (6.0, range 3.0–8.0) (P0.05). Most participants (95%) responded that their understanding of hereditary breast cancer had increased after the group genetic counseling session and that their satisfaction was high. The main advantage noted with metaverse was no limit of space and location while attending the session (97%), and the main disadvantage was a possibility of missing content due to an unstable internet connection (67%). Conclusions: The metaverse platform would be acceptable as an alternative group genetic counseling service. More studies are needed to investigate how, for whom, and in what circumstances metaverse can be effectively utilized.

  • Original Article2024-05-01 Diagnostic Genetics

    Association Between Aortic Valve Sclerosis and Clonal Hematopoiesis of Indeterminate Potential

    Minkwan Kim , M.D., Ph.D., Jin Ju Kim , M.D., Ph.D., Seung-Tae Lee , M.D., Ph.D., Yeeun Shim , M.S., Hyeonah Lee , Ph.D., SungA Bae , M.D., Ph.D., Nak-Hoon Son , Ph.D., Saeam Shin , M.D., Ph.D., and In Hyun Jung , M.D., Ph.D.

    Ann Lab Med 2024; 44(3): 279-288

    Abstract : Background: The mechanism and medical treatment target for degenerative aortic valve disease, including aortic stenosis, is not well studied. In this study, we investigated the effect of clonal hematopoiesis of indeterminate potential (CHIP) on the development of aortic valve sclerosis (AVS), a calcified aortic valve without significant stenosis. Methods: Participants with AVS (valves ≥2 mm thick, high echogenicity, and a peak transaortic velocity of

  • Brief Communication2024-05-01 Diagnostic Genetics

    Optimization of a Protocol for Isolating Cell-free DNA From Cerebrospinal Fluid

    Ho Hyun Song , M.S., Hyeran Park , M.D., Ph.D., Doohwan Cho , M.S., Hae In Bang , M.D., Ph.D., Hyuk-Jin Oh , M.D., and Jieun Kim , M.D., Ph.D.

    Ann Lab Med 2024; 44(3): 294-298

    Abstract : A standardized protocol for the isolation of cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) is lacking. Therefore, we established a cfDNA isolation protocol optimized for clinical CSF specimens, integrating acceptable modifications and using artificial CSF generated from remnant CSF spiked with reference cell-free tumor DNA (ctDNA). We compared the isolation yields of in vitro diagnostic (IVD)-certified column-based (CB) and magnetic bead-based (MB) isolation. Furthermore, we modified both methods, including pre- and post-elution steps. To confirm ctDNA integrity and quantify the variant allele frequency after isolation, we performed droplet digital PCR (ddPCR) targeting IDH1 R132C in the reference ctDNA. MB isolation had a higher yield than CB isolation (P

  • Original Article2024-07-01 Diagnostic Genetics

    TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism

    Hai-Yang Zhang , M.D., Feng-Yao Wu , M.D., Xue-Song Li , M.D., Ping-Hui Tu , M.D., Cao-Xu Zhang , M.D., Rui-Meng Yang , M.D., Ph.D., Ren-Jie Cui , Ph.D., Chen-Yang Wu , M.D., Ya Fang , M.D., Ph.D., Liu Yang , M.S., Huai-Dong Song , M.D., Ph.D., and Shuang-Xia Zhao , M.D., Ph.D.

    Ann Lab Med 2024; 44(4): 343-353

    Abstract : Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions: We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

  • Original Article2024-05-01 Diagnostic Genetics

    Re-evaluation of a Fibrillin-1 Gene Variant of Uncertain Significance Using the ClinGen Guidelines

    Seo Wan Kim , M.D., Boyeon Kim , M.D., Ph.D., Yoonjung Kim , M.D., Ph.D., and Kyung-A Lee , M.D., Ph.D.

    Ann Lab Med 2024; 44(3): 271-278

    Abstract : Background: Marfan syndrome (MFS) is caused by fibrillin-1 gene (FBN1) variants. Mutational hotspots and/or well-established critical functional domains of FBN1 include cysteine residues, calcium-binding consensus sequences, and amino acids related to interdomain packaging. Previous guidelines for variant interpretation do not reflect the features of genes or related diseases. Using the Clinical Genome Resource (ClinGen) FBN1 variant curation expert panel (VCEP), we re-evaluated FBN1 germline variants reported as variants of uncertain significance (VUSs). Methods: We re-evaluated 26 VUSs in FBN1 reported in 161 patients with MFS. We checked the variants in the Human Genome Mutation Database, ClinVar, and VarSome databases and assessed their allele frequencies using the gnomAD database. Patients’ clinical information was reviewed. Results: Four missense variants affecting cysteines (c.460T>C, c.1006T>C, c.5330G>C, and c.8020T>C) were reclassified as likely pathogenic and were assigned PM1_strong or PM1. Two intronic variants were reclassified as benign by granting BA1 (stand-alone). Four missense variants were reclassified as likely benign. BP5 criteria were applied in cases with an alternate molecular basis for disease, one of which (c.7231G>A) was discovered alongside a pathogenic de novo COL3A1 variant (c.1988G>T, p.Gly633Val). Conclusions: Considering the high penetrance of FBN1 variants and clinical variability of MFS, the detection of pathogenic variants is important. The ClinGen FBN1 VCEP encompasses mutational hotspots and/or well-established critical functional domains and adjusts the criteria specifically for MFS; therefore, it is beneficial not only for identifying pathogenic FBN1 variants but also for distinguishing these variants from those that cause other connective tissue disorders with overlapping clinical features.

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Annals of Laboratory Medicine
Journal Information March, 2025
Vol.45 No.2
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