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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 300 - 312 (13page)
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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.
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참고문헌 (32)
참고문헌 신청
Vermorken JB / 2007 / Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy / J Clin Oncol 25:2171~2177
Chow LQ / 2016 / Antitumor activity of pembrolizumab in biomarkerunselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma : results from the phase Ib KEYNOTE-012 Expansion Cohort / J Clin Oncol 34:3838~3845
Agrawal N / 2011 / Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1 / Science 333:1154~1157
Stransky N / 2011 / The mutational landscape of head and neck squamous cell carcinoma / Science 333:1157~1160
Cancer Genome Atlas Network / 2015 / Comprehensive genomic characterization of head and neck squamous cell carcinomas / Nature 517:576~582
Chow LQ / 2016 / Antitumor activity of pembrolizumab in biomarkerunselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma : results from the phase Ib KEYNOTE-012 Expansion Cohort / J Clin Oncol 34:3838~3845
Agrawal N / 2011 / Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1 / Science 333:1154~1157
Stransky N / 2011 / The mutational landscape of head and neck squamous cell carcinoma / Science 333:1157~1160
Cancer Genome Atlas Network / 2015 / Comprehensive genomic characterization of head and neck squamous cell carcinomas / Nature 517:576~582
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