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.