149 197

Cited 11 times in

Investigating the Feasibility of Targeted Next-Generation Sequencing to Guide the Treatment of Head and Neck Squamous Cell Carcinoma

Authors
 Sun Min Lim  ;  Sang Hee Cho  ;  In Gyu Hwang  ;  Jae Woo Choi  ;  Hyun Chang  ;  Myung-Ju Ahn  ;  Keon Uk Park  ;  Ji-Won Kim  ;  Yoon Ho Ko  ;  Hee Kyung Ahn  ;  Byoung Chul Cho  ;  Byung-Ho Nam  ;  Sang Hoon Chun  ;  Ji Hyung Hong  ;  Jung Hye Kwon  ;  Jong Gwon Choi  ;  Eun Joo Kang  ;  Tak Yun  ;  Keun-Wook Lee  ;  Joo-Hang Kim  ;  Jin Soo Kim  ;  Hyun Woo Lee  ;  Min Kyoung Kim  ;  Dongmin Jung  ;  Ji Eun Kim  ;  Bhumsuk Keam  ;  Hwan Jung Yun  ;  Sangwoo Kim  ;  Hye Ryun Kim 
Citation
 Cancer Research and Treatment, Vol.51(1) : 300-312, 2019 
Journal Title
 Cancer Research and Treatment 
ISSN
 1598-2998 
Issue Date
2019
MeSH
Adult ; Aged ; Aged, 80 and over ; Cadherins/genetics ; Class I Phosphatidylinositol 3-Kinases/genetics ; Cyclin D1/genetics ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Feasibility Studies ; Female ; Genetic Predisposition to Disease ; Head and Neck Neoplasms/genetics* ; Head and Neck Neoplasms/virology ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Male ; Middle Aged ; Molecular Targeted Therapy ; Mutation ; Papillomaviridae ; Papillomavirus Infections/genetics* ; Receptor, Notch1/genetics ; Republic of Korea ; Sequence Analysis, DNA/methods* ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Squamous Cell Carcinoma of Head and Neck/virology ; Tumor Suppressor Protein p53/genetics
Keywords
Biomarkers ; Clinical trial ; Molecular Targeted Therapy ; Next-generation sequencing ; Squamous cell carcinoma of the head and neck
Abstract
PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. Materials and Methods: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)-negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.
Files in This Item:
T201902557.pdf Download
DOI
10.4143/crt.2018.012
Appears in Collections:
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
Yonsei Authors
Kim, Sangwoo(김상우) ORCID logo https://orcid.org/0000-0001-5356-0827
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/170988
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links