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Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer

Authors
 Han Na Kang  ;  Jae-Hwan Kim  ;  A-Young Park  ;  Jae Woo Choi  ;  Sun Min Lim  ;  Jinna Kim  ;  Eun Joo Shin  ;  Min Hee Hong  ;  Kyoung-Ho Pyo  ;  Mi Ran Yun  ;  Dong Hwi Kim  ;  Hanna Lee  ;  Sun Och Yoon  ;  Da Hee Kim  ;  Young Min Park  ;  Hyung Kwon Byeon  ;  Inkyung Jung  ;  Soonmyung Paik  ;  Yoon Woo Koh  ;  Byoung Chul Cho  ;  Hye Ryun Kim 
Citation
 BMC CANCER, Vol.20(1) : 316, 2020-04 
Journal Title
 BMC CANCER 
Issue Date
2020-04
Keywords
Biomarker ; Head and neck cancer ; Patient-derived xenograft ; Squamous cell cancer
Abstract
Background: We investigated whether head and neck squamous cell carcinoma (HNSCC) patient-derived xenografts (PDXs) reaffirm patient responses to anti-cancer therapeutics. Methods: Tumors from HNSCC patients were transplanted into immunodeficient mice and propagated via subsequent implantation. We evaluated established PDXs by histology, genomic profiling, and in vivo anti-cancer efficacy testing to confirm them as the authentic in vivo platform. Results: From 62 HNSCCs, 15 (24%) PDXs were established. The primary cancer types were tongue (8), oropharynx (3), hypopharynx (1), ethmoid sinus cancer (1), supraglottic cancer (1), and parotid gland (1); six PDXs (40%) were established from biopsy specimens from advanced HNSCC. PDXs mostly retained donor characteristics and remained stable across passages. PIK3CA (H1047R), HRAS (G12D), and TP53 mutations (H193R, I195T, R248W, R273H, E298X) and EGFR, CCND1, MYC, and PIK3CA amplifications were identified. Using the acquisition method, biopsy showed a significantly higher engraftment rate when compared with that of surgical resection (100% [6/6] vs. 16.1% [9/56], P < 0.001). Specimens obtained from metastatic sites showed a significantly higher engraftment rate than did those from primary sites (100% [9/9] vs. 11.3% [6/53], P < 0.001). Three PDX models from HPV-positive tumors were established, as compared to 12 from HPV-negative (15.8% [3/19] and 27.9% [12/43] respectively, P = 0.311), suggesting that HPV positivity tends to show a low engraftment rate. Drug responses in PDX recapitulated the clinical responses of the matching patients with pan-HER inhibitors and pan-PI3K inhibitor. Conclusions: Genetically and clinically annotated HNSCC PDXs could be useful preclinical tools for evaluating biomarkers, therapeutic targets, and new drug discovery.
Files in This Item:
T202002780.pdf Download
DOI
10.1186/s12885-020-06786-5
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Koh, Yoon Woo(고윤우)
Kim, Da Hee(김다희) ORCID logo https://orcid.org/0000-0001-7286-1334
Kim, Jinna(김진아) ORCID logo https://orcid.org/0000-0002-9978-4356
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Park, Young Min(박영민) ORCID logo https://orcid.org/0000-0002-7593-8461
Paik, Soon Myung(백순명) ORCID logo https://orcid.org/0000-0001-9688-6480
Lee, Hanna(이한나)
Lim, Sun Min(임선민)
Jung, Inkyung(정인경) ORCID logo https://orcid.org/0000-0003-3780-3213
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Pyo, Kyoung Ho(표경호) ORCID logo https://orcid.org/0000-0001-5428-0288
Hong, Min Hee(홍민희) ORCID logo https://orcid.org/0000-0003-3490-2195
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/179099
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