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Genomic comparison between an in vitro three-dimensional culture model of melanoma and the original primary tumor

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Abstract

Three-dimensional (3D) melanoma culture is a personalized in vitro model that can be used for high-fidelity pre-clinical testing and validation of novel therapies. However, whether the genomic landscape of 3D cultures faithfully reflects the original primary tumor which remains unknown. The purpose of our study was to compare the genomic landscapes of 3D culture models with those of the original tumors. Patient-derived xenograft (PDX) tumors were established by engrafting fresh melanoma tissue from each patient. Then, a 3D culture model was generated using cryopreserved PDX tumors embedded in pre-gelled porcine skin decellularized extracellular matrix with normal human dermal fibroblasts. Using whole-exome sequencing, the genomic landscapes of 3D cultures, PDX tumors, and the original tumor were compared. We found that 91.4% of single-nucleotide variants in the original tumor were detected in the 3D culture and PDX samples. Putative melanoma driver mutations (BRAF p.V600E, CDKN2A p.R7*, ADAMTS1 p.Q572*) were consistently identified in both the original tumor and 3D culture samples. Genome-wide copy number alteration profiles were almost identical between the original tumor and 3D culture samples, including the driver events of ARID1B loss, BRAF gain, and CCND1 gain. In conclusion, our study revealed that the genomic profiles of the original tumor and our 3D culture model showed high concordance, indicating the reliability of our 3D culture model in reflecting the original characteristics of the tumor.

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Data availability

Raw sequencing data were deposited in the Sequence Read Archive (SRA) database (Project ID: PRJNA813613).

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Acknowledgements

This study was supported by grants from National Research Foundation of Korea (2020R1C1C11011296, RS-2022-00165497, and 2019R1A5A2027588). This research was supported by a grant of the MD-Phd/Medical Scientist Training Program through the Korea Health Industry Development Institue (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea. The biospecimens for this study were provided by The Biobank of Seoul St. Mary's Hospital, the Catholic University of Korea. 

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Authors and Affiliations

  1. Precision Medicine Research Center, The Catholic University of Korea, Seoul, Republic of Korea

    Yoon-Seob Kim & Yeun-Jun Chung

  2. IRCGP, The Catholic University of Korea, Seoul, Republic of Korea

    Yoon-Seob Kim & Yeun-Jun Chung

  3. Department of Microbiology, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, Republic of Korea

    Yoon-Seob Kim & Yeun-Jun Chung

  4. T&R Biofab Co.Ltd., Seongnam-Si, Republic of Korea

    Minji Park

  5. Department of Mechanical Engineering, Tech University of Korea, Siheung-Si, Republic of Korea

    Songwan Jin

  6. Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Ga Hee Jeong & Yeun-Jun Chung

  7. Department of Dermatology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, Republic of Korea

    Chul Hwan Bang

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  1. Yoon-Seob Kim
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Contributions

Conception and design: Y.-J. Chung, C.-H. Bang Development of methodology: S. Jin, Y.-J. Chung, C.-H. Bang Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): All authors Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): All authors Writing, review, and/or revision of the manuscript: Y.-S. Kim, Y.-J. Chung, C.-H. Bang Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): Y.-J. Chung, C.-H. Bang Study supervision: Y.-J. Chung, C.-H. Bang

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Correspondence to Yeun-Jun Chung or Chul Hwan Bang.

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Kim, YS., Park, M., Jin, S. et al. Genomic comparison between an in vitro three-dimensional culture model of melanoma and the original primary tumor. Arch Dermatol Res 315, 1225–1231 (2023). https://doi.org/10.1007/s00403-022-02502-4

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  • DOI: https://doi.org/10.1007/s00403-022-02502-4

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