2018 AHNS Meeting Abstracts

Comparing Mutational Profiles of Responders and Non-responders Cell-Free Circulating Tumor DNA in Oropharyngeal Squamous Cell Carcinoma Patients

Presentation:	C051
Topic:	Pharynx / Larynx Cancer
Type:	Poster
Date:	Thursday, April 19, 2018
Session:	9:00 AM - 7:00 PM
Authors:	Mickie J Hamiter, MD¹, Adam H Greer, PhD², Rhett Orgeron¹, Alok R Khandelwal, PhD¹, Xiaohui Ma¹, Tara Moore-Medlin¹, Hong Yin, MDPhD², Glenn Mills, MD², Cherie-Ann O Nathan, MD¹
Institution(s):	¹LSU Health Shreveport, ²Feist Weiller Cancer Center

INTRODUCTION: Circulating tumor DNA (ctDNA) genotyping is quickly becoming a new and effective diagnostic tool that offers several advantages over traditional tissue biopsies in assessing the likelihood of cancer recurrence and treatment outlook.

OBJECTIVE: Our goal was to determine if somatic non-synonymous variants could be identified in cell-free DNA (cfDNA) of Oropharyngeal Squamous Carcinoma patients with matched tumor tissue and if these variants could predict treatment response.

STUDY DESIGN: Retrospective. 28 patients were classified as responder and non-responder groups according to the patient database.

METHODS: Genomic DNA was isolated from 28 Oropharyngeal SCC patients’ tumors using NucleoSpin Tissue kit from Clontech. Matched cfDNA was extracted from plasma using Zymo’s Quick-cfDNATM Serum and Plasma kit. The quality and size of DNA was determined by Agilent 2200 tapestation and quantified using qPCR. Libraries were prepared with Accel-Amplicon 56G Oncology Panel of Swift Biosciences. DNA sequencing was then performed using the Illumina MiSeq platform. Variants were identified using Biomedical Genomic Workbench.

RESULTS: From the 28 matched samples 8 somatic non-synonymous variants were found in both tissue and plasma, 7 of which were present in patients that were non-responders. The variants were in 3 genes TP53, HNF1A, and FBXW7. The variants and their frequencies in the non-responder group were as follows (tumor DNA /cfDNA in %) TP53 Gly325fs (26.98/0.62), TP53 Arg282Trp (48.05/1.74), HNF1A 864delGinsCC (6.45/2.34), FBXW7 Arg505Gly (30.46/0.6), FBXW7 Arg505Leu (30.94/0.65), TP53 Arg273Cys (38.68/2.18), and one variant in the responder group TP53 Arg196* (90.27/0.81). Additionally, only 7% of HPV positive patients had matching variants while 55% of HPV negative patients had matching variants.

CONCLUSION: Somatic non-synonymous variants can be identified in cfDNA of Oropharyngeal Squamous Carcinoma patients using NGS. The detected variants in cfDNA were more frequent in non-responders and HPV negative patients. This finding could be helpful in developing personalized treatment.

AHNS Annual Meeting

Held during the Combined Otolaryngology Spring Meetings (COSM)

April 18–19, 2018
Gayloard National Resort
and Convention Center
National Harbor, MD

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