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

被引:12
|
作者
Song, Haa-Na [1 ,6 ]
Lee, Chung [2 ,7 ]
Kim, Seung Tae [1 ]
Kim, Sun Young [1 ]
Kim, Nayoung K. D. [2 ]
Jang, Jiryeon [1 ]
Kang, Mihyun [1 ]
Jang, Hyojin [1 ]
Ahn, Soomin [3 ]
Kim, Seok Hyeong [3 ]
Park, Yoona [4 ]
Cho, Yong Beom [4 ]
Heo, Jeong Wook [4 ]
Lee, Woo Yong [4 ]
Park, Joon Oh [1 ]
Lim, Ho Yeong [1 ]
Kang, Won Ki [1 ]
Park, Young Suk [1 ]
Park, Woong-Yang [2 ,5 ,7 ]
Lee, Jeeyun [1 ]
Kim, Hee Cheol [4 ]
机构
[1] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med,Div Hematol Oncol, Seoul, South Korea
[2] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Samsung Genome Inst, Seoul, South Korea
[3] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol & Translat Genom, Seoul, South Korea
[4] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Surg, Seoul, South Korea
[5] Sungkyunkwan Univ, Sch Med, Dept Mol Cell Biol, Seoul, South Korea
[6] Gyeongsang Natl Univ, Sch Med, Dept Internal Med, Jinju, South Korea
[7] Sungkyunkwan Univ, SAIHST, Dept Hlth Sci & Technol, Seoul, South Korea
关键词
colorectal cancer; patient-derived cell; somatic mutation; III COLON-CANCER; XENOGRAFT MODELS; STAGE-II; MUTATION; OXALIPLATIN; CETUXIMAB; BIOLOGY; KRAS; BRAF;
D O I
10.18632/oncotarget.7526
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:19610 / 19619
页数:10
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