Investigating the Feasibility of Targeted Next-Generation Sequencing to Guide the Treatment of Head and Neck Squamous Cell Carcinoma
| Autor: | Eun Joo Kang, Sun Min Lim, Yoon Ho Ko, Joo Hang Kim, Sangwoo Kim, Byoung Chul Cho, Hee Kyung Ahn, Hyun Chang, Dongmin Jung, Byung-Ho Nam, Keun-Wook Lee, Hye Ryun Kim, Jung Hye Kwon, Ji Eun Kim, Sang-Hee Cho, In Gyu Hwang, Myung-Ju Ahn, Keon Uk Park, Ji Hyung Hong, Sang Hoon Chun, Hwan Jung Yun, Jae Woo Choi, Tak Yun, Min Kyoung Kim, Jong Gwon Choi, Hyun Woo Lee, Ji Won Kim, Bhumsuk Keam, Jin-Soo Kim |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research medicine.medical_treatment medicine.disease_cause Targeted therapy 0302 clinical medicine CDKN2A Medicine Cyclin D1 Molecular Targeted Therapy Receptor Notch1 Papillomaviridae Aged 80 and over Mutation biology High-Throughput Nucleotide Sequencing Middle Aged Cadherins Clinical trial Head and Neck Neoplasms Squamous cell carcinoma of the head and neck 030220 oncology & carcinogenesis Original Article Female medicine.drug Adult medicine.medical_specialty Class I Phosphatidylinositol 3-Kinases DNA sequencing 03 medical and health sciences Internal medicine Republic of Korea Humans Genetic Predisposition to Disease neoplasms Cyclin-Dependent Kinase Inhibitor p16 Aged Cisplatin Squamous Cell Carcinoma of Head and Neck business.industry Papillomavirus Infections Sequence Analysis DNA biology.organism_classification Precision medicine medicine.disease Head and neck squamous-cell carcinoma stomatognathic diseases 030104 developmental biology Next-generation sequencing Feasibility Studies Tumor Suppressor Protein p53 business Biomarkers |
| Zdroj: | Cancer Research and Treatment : Official Journal of Korean Cancer Association |
| ISSN: | 2005-9256 1598-2998 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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