domingo, 20 de mayo de 2018

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

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



 2018 May 9. doi: 10.4143/crt.2018.012. [Epub ahead of print]

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

Lim SM1Cho SH2Hwang IG3Choi JW4Chang H5Ahn MJ6Park KU7Kim JW8Ko YH9Ahn HK10Cho BC11Nam BH12Chun SH13Hong JH14Kwon JH15Choi JG16Kang EJ17Yun T18Lee KW8Kim JH1Kim JS19Lee HW20Kim MK21Jung D22Kim JE23Keam B24Yun HJ25Kim S26Kim HR11.

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 (15%) patients.

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.

KEYWORDS:

Biomarkers; Clinical trial; Molecular Targeted Therapy; Next-generation sequencing; Squamous cell carcinoma of the head and neck

PMID:
 
29747488
 
DOI:
 
10.4143/crt.2018.012
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