2714 - The Genomic Landscape of Human Papillomavirus Positive Early-Stage Oropharyngeal Carcinoma
Presenter(s)
M. H. Brown1, W. Mendes2, Y. Song3, A. Shetty4, M. E. Witek1, R. Mehra5, K. Hatten6, R. Taylor6, K. Moyer6, J. Wolf6, T. N. Tyer7, K. Steacy7, C. Eggleston1, C. Datnow-Martinez1, D. Gaykalova8, W. F. Regine Jr1, L. Ren3, P. T. Tran3, M. J. Ferris1, and J. K. Molitoris1; 1Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, 2University of Maryland, Baltimore, MD, 3University of Maryland School of Medicine, Baltimore, MD, 4Department of Radiation Oncology, Division of Translational Radiation Sciences, University of Maryland Baltimore, School of Medicine,, Baltimore, MD, 5University of Maryland Cancer Center, Baltimore, MD, 6Department of Otorhinolaryngology – Head & Neck Surgery, University of Maryland School of Medicine, Baltimore, MD, 7Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, 8University of Maryland School of Medicine, BALTIMORE, MD
Purpose/Objective(s):
The genomic landscape of human papillomavirus positive (HPV+) oropharyngeal cancer (OPX) remains very limited. There is greater appreciation of the genomic landscape in more advanced HPV+ OPX. A better understanding of the differences between early and late-stage disease may improve elucidation of risk factors that warrant de-escalation. This analysis aims to substantially contribute to the existing knowledge of the genomic landscape in an exclusively stage group I/II cohort.Materials/Methods:
NGS DNA mutational profiling (648-gene panel) was performed on 37 samples of p16+ OPX (24 stage I, 13 stage II). Somatic nonsynonymous pathogenic mutations were identified using Mutect2 and ClinVAR database. Mutational rates of a 107-patient cohort from the literature of largely advanced stage and metastatic p16+ OPX is reported as a reference.Results:
Patients had a median age of 64 (41-79) and a majority were male (33, 89%), white (31, 83.8%) with a smoking history (19, 52%), T2-T3 (28, 76%) and node positive (33, 89%). A total of 582 nonsynonymous somatic mutations [including 488 single-nucleotide polymorphism (SNPs) and 76 INDELs involved in 308 genes] were identified with a median of 12 mutations per sample. The median tumor mutation burden per sample is 5 mutations/Mb. Among them, 37 pathogenic/likely pathogenic somatic mutations were annotated using ClinVAR database which include 33 SNPs and 8 INDELs involved in 4 genes. The top10 pathogenic/likely pathogenic mutated genes were PIK3CA, RB1, FBXW7, FGFR3, TP53, CYLD, B2M, FLCN, FGF23, and ERBB2. All nonsynonymous mutations are compared to literature in Table 1.Conclusion:
In this study, the genomic landscape of early stage p16+ OPX shows comparable mutational frequencies of known associated genes in advanced/metastatic stages, including PIK3CA, FGFR3 and FBXW7. This early-stage cohort contained higher than expected RB1 and KMT2D mutations, both of which have been posited to play a role in epigenetic modification. Abstract 2714 - Table 1: Comparison of all nonsynonymous mutation frequencies| Gene | Our cohort | Literature Cohort |
| PIK3CA | 27% | 22% |
| KMT2D | 30% | 8% |
| RB1 | 16% | 4% |
| FANCA | 14% | 3% |
| NOTCH1 | 14% | 4% |
| BRCA2 | 11% | 3% |
| PRKDC | 14% | 7% |
| FBXW7 | 14% | 8% |
| CYLD | 11% | 7% |
| NF1 | 8% | 3% |
| FGFR3 | 8% | 7% |
| TP53 | 8% | 9% |
| PTEN | 3% | 9% |