Oncotarget

Research Papers:

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

Haa-Na Song, Chung Lee, Seung Tae Kim, Sun Young Kim, Nayoung K.D. Kim, Jiryeon Jang, Mihyun Kang, Hyojin Jang, Soomin Ahn, Seok Hyeong Kim, Yoona Park, Yong Beom Cho, Jeong Wook Heo, Woo Yong Lee, Joon Oh Park, Ho Yeong Lim, Won Ki Kang, Young Suk Park, Woong-Yang Park, Jeeyun Lee and Hee Cheol Kim _

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Oncotarget. 2016; 7:19610-19619. https://doi.org/10.18632/oncotarget.7526

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Abstract

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

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.


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