Molecular characterization of colorectal cancer patients and concomitant patient-derived tumor cell establishment
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Haa-Na Song1,6,*, Chung Lee2,7,*, Seung Tae Kim1, Sun Young Kim1, Nayoung K.D. Kim2, Jiryeon Jang1, Mihyun Kang1, Hyojin Jang1, Soomin Ahn3, Seok Hyeong Kim3, Yoona Park4, Yong Beom Cho4, Jeong Wook Heo4, Woo Yong Lee4, Joon Oh Park1, Ho Yeong Lim1, Won Ki Kang1, Young Suk Park1, Woong-Yang Park2,5,7, Jeeyun Lee1, Hee Cheol Kim4
1Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2Samsung Genome Institute, Samsung Medical Center, Seoul, Korea
3Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
4Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
5Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Korea
6Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea
7Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea
*These authors contributed equally to this work
Hee Cheol Kim, e-mail: [email protected]
Jeeyun Lee, e-mail: [email protected]
Woong-Yang Park, e-mail: [email protected]
Keywords: colorectal cancer, patient-derived cell, somatic mutation
Received: October 14, 2015 Accepted: January 18, 2016 Published: February 20, 2016
Background: We aimed to establish a prospectively enrolled colorectal cancer (CRC) cohort for targeted sequencing of primary tumors from CRC patients. In parallel, we established collateral PDC models from the matched primary tumor tissues, which may be later used as preclinical models for genome-directed targeted therapy experiments.
Results: In all, we identified 27 SNVs in the 6 genes such as PIK3CA (N = 16), BRAF (N = 6), NRAS (N = 2), and CTNNB1 (N = 1), PTEN (N = 1), and ERBB2 (N = 1). RET-NCOA4 translocation was observed in one out of 105 patients (0.9%). PDC models were successfully established from 62 (55.4%) of the 112 samples. To confirm the genomic features of various tumor cells, we compared variant allele frequency results of the primary tumor and progeny PDCs. The Pearson correlation coefficient between the variants from primary tumor cells and PDCs was 0.881.
Methods: Between April 2014 and June 2015, 112 patients with CRC who underwent resection of the primary tumor were enrolled in the SMC Oncology Biomarker study. The PDC culture protocol was performed for all eligible patients. All of the primary tumors from the 112 patients who provided written informed consent were genomically sequenced with targeted sequencing. In parallel, PDC establishment was attempted for all sequenced tumors.
Conclusions: We have prospectively sequenced a CRC cohort of 105 patients and successfully established 62 PDC in parallel. Each genomically characterized PDCs can be used as a preclinical model especially in rare genomic alteration event.
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