Work

Molecular characterization of colorectal cancer patients and concomitant patient-derived tumor cell establishment

Year: 2016
Type: article
Study design: Observational Study
Abstract: // Haa-Na Song 1, 6, * , Chung Lee 2, 7, * , Seung Tae Kim 1 , Sun Young Kim 1 , Nayoung K.D. Kim 2 , Jiryeon Jang 1 , Mihyun Kang 1 , Hyojin Jang 1 , Soomin Ahn 3 , Seok Hyeong Kim 3 , Yoona Park 4 , Yong Beom Cho 4 , Jeong Wook Heo 4 , Woo Yong Lee 4 , Joon Oh Park 1 , Ho Yeong Lim 1 , Won Ki Kang 1 , Young Suk Park 1 , Woong-Yang Park 2, 5, 7 , Jeeyun Lee 1 , Hee Cheol Kim 4 1 Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Samsung Genome Institute, Samsung Medical Center, Seoul, Korea 3 Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 4 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 5 Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Korea 6 Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea 7 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea * These authors contributed equally to this work Correspondence to: 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 ABSTRACT 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.
Source: Oncotarget
Language: English
Subfield: Oncology
Field: Medicine
Open Access status: diamond
Funder: Samsung
OpenAlex ID: W2315761086
FWCI: 1.257
Cites: 31
Cited by: 14
Related to: 10