Cancer Research and Treatment

Original Articles

General

Target-Enhanced Whole-Genome Sequencing Shows Clinical Validity Equivalent to Commercially Available Targeted Oncology Panel: Sangmoon Lee, Jin Roh, Jun Sung Park, Islam Oguz Tuncay, Wonchul Lee, Jung-Ah Kim, Brian Baek-Lok Oh, Jong-Yeon Shin, Jeong Seok Lee, Young Seok Ju, Ryul Kim, Seongyeol Park, Jaemo Koo, Hansol Park, Joonoh Lim, Erin Connolly-Strong, Tae-Hwan Kim, Yong Won Choi, Mi Sun Ahn, Hyun Woo Lee, Seokhwi Kim, Jang-Hee Kim, Minsuk Kwon; Cancer Res Treat. 2025;57(2):350-361. Published online September 19, 2024; DOI: https://doi.org/10.4143/crt.2024.114

Abstract PDF Supplementary Material PubReader ePub: Purpose
Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS.
Materials and Methods
This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches.
Results
TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making.
Conclusion
TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

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Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer: In Hye Song, Sun-Hee Heo, Won Seon Bang, Hye Seon Park, In Ah Park, Young-Ae Kim, Suk Young Park, Jin Roh, Gyungyub Gong, Hee Jin Lee; Cancer Res Treat. 2017;49(2):399-407. Published online July 27, 2016; DOI: https://doi.org/10.4143/crt.2016.215

Abstract PDF Supplementary Material PubReader ePub

Purpose
The tertiary lymphoid structure (TLS) is an important source of tumor-infiltrating lymphocytes (TILs), which have a strong prognostic and predictive value in triple-negative breast cancer (TNBC). A previous study reported that the levels of CXCL13 mRNA expression were associated with TLSs, but measuring the gene expression is challenging in routine practice. Therefore, this study evaluated the MECA79-positive high endothelial venule (HEV) densities and their association with the histopathologically assessed TLSs in biopsy samples. In addition, the relationship of TLSs with the CXCL13 transcript levels and clinical outcomes were examined.
Materials and Methods
A total of 108 TNBC patients treated with neoadjuvant chemotherapy (NAC) were studied. The amounts of TILs and TLSs were measured histopathologically using hematoxylin and eosin–stained slides. The HEV densities and TIL subpopulations were measured by immunohistochemistry for MECA79, CD3, CD8, and CD20. CXCL13 mRNA expression levels using a NanoString assay (NanoString Technologies).
Results
The mean number of HEVs in pre-NAC biopsies was 12 (range, 0 to 72). The amounts of TILs and TLSs, HEV density, and CXCL13 expression showed robust correlations with each other. A lower pre-NAC clinical T stage, higher TIL and TLS levels, a higher HEV density, CD20-positive cell density, and CXCL13 expression were significant predictors of a pathologic complete response (pCR). Higher CD8-positive cell density and levels of CXCL13 expression were significantly associated with a better disease-free survival rate.
Conclusion
MECA79-positive HEV density in pre-NAC biopsies is an objective and quantitative surrogate marker of TLS and might be a valuable tool for predicting pCR of TNBC in routine pathology practice.

Citations

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Preliminary Suggestion about Staging of Anorectal Malignant Melanoma May Be Used to Predict Prognosis: Won Young Chae, Jong Lyul Lee, Dong-Hyung Cho, Chang Sik Yu, Jin Roh, Jin Cheon Kim; Cancer Res Treat. 2016;48(1):240-249. Published online March 6, 2015; DOI: https://doi.org/10.4143/crt.2014.305

Abstract PDF PubReader ePub

Purpose
Anorectal malignant melanomas (AMM) are rare and have poor survival. The study aims to evaluate the clinicopathologic characteristics and outcomes of patients with AMM, and to devise a staging system predictive of survival outcome.
Materials and Methods
This was a retrospective study of 28 patients diagnosed with, and treated for AMM. Patients classified by clinical staging of mucosal melanoma (MM) were reclassified via rectal and anal TNM staging. Survival outcomes were compared among patients grouped by the three different staging systems.
Results
The three staging systems were equated with similar figures for 5-year overall survival (OS) and 5-year disease-free survival (DFS) of patients diagnosed with stage I disease. Patients (n=19) diagnosed with MM stage II disease were reclassified by rectal TNM staging into three subgroups: IIIA, IIIB, and IIIC. For these patients, both 5-year OS and 5-year DFS differed significantly between the subgroups IIIA and IIIC (OS: IIIA vs. IIIC, 66.7% vs. 0%, p=0.002; DFS: IIIA vs. IIIC, 51.4% vs. 0%, p < 0.001).
Conclusion
The accuracy of prognosis in patients diagnosed with AMM and lymph node metastasis has improved by using rectal TNM staging, which includes information regarding the number of lymph node metastases.

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