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

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.

• 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
• Journal: Cancer research and treatment (Cancer Res Treat) Vol. 51 Issue 1 Pg. 300-312 (Jan 2019) ISSN: 2005-9256 [Electronic] Korea (South)
• PMID: 29747488 (Publication Type: Journal Article, Multicenter Study)

Chemical References

• CCND1 protein, human
• CDKN2A protein, human
• Cadherins
• Cyclin-Dependent Kinase Inhibitor p16
• FAT1 protein, human
• NOTCH1 protein, human
• Receptor, Notch1
• TP53 protein, human
• Tumor Suppressor Protein p53
• Cyclin D1
• Class I Phosphatidylinositol 3-Kinases
• PIK3CA protein, human

Topics

• 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, 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, virology)
• Tumor Suppressor Protein p53 (genetics)