Signatures of somatic mutations and gene expression from p16INK4A positive head and neck squamous cell carcinomas (HNSCC).
Nabil F SabaAshok R DinasarapuKelly R MaglioccaBhakti DwivediSandra SebyZhaohui S QinMihir PatelChristopher C GriffithXu WangMark El-DeiryConor Ernst SteuerJeanne KowalskiDong Moon ShinMichael E ZwickZhuo Georgia ChenPublished in: PloS one (2020)
Human papilloma virus (HPV) causes a subset of head and neck squamous cell carcinomas (HNSCC) of the oropharynx. We combined targeted DNA- and genome-wide RNA-sequencing to identify genetic variants and gene expression signatures respectively from patients with HNSCC including oropharyngeal squamous cell carcinomas (OPSCC). DNA and RNA were purified from 35- formalin fixed and paraffin embedded (FFPE) HNSCC tumor samples. Immuno-histochemical evaluation of tumors was performed to determine the expression levels of p16INK4A and classified tumor samples either p16+ or p16-. Using ClearSeq Comprehensive Cancer panel, we examined the distribution of somatic mutations. Somatic single-nucleotide variants (SNV) were called using GATK-Mutect2 ("tumor-only" mode) approach. Using RNA-seq, we identified a catalog of 1,044 and 8 genes as significantly expressed between p16+ and p16-, respectively at FDR 0.05 (5%) and 0.1 (10%). The clinicopathological characteristics of the patients including anatomical site, smoking and survival were analyzed when comparing p16+ and p16- tumors. The majority of tumors (65%) were p16+. Population sequence variant databases, including gnomAD, ExAC, COSMIC and dbSNP, were used to identify the mutational landscape of somatic sequence variants within sequenced genes. Hierarchical clustering of The Cancer Genome Atlas (TCGA) samples based on HPV-status was observed using differentially expressed genes. Using RNA-seq in parallel with targeted DNA-seq, we identified mutational and gene expression signatures characteristic of p16+ and p16- HNSCC. Our gene signatures are consistent with previously published data including TCGA and support the need to further explore the biologic relevance of these alterations in HNSCC.
Keyphrases
- squamous cell
- genome wide
- copy number
- rna seq
- single cell
- dna methylation
- gene expression
- high grade
- circulating tumor
- single molecule
- cell free
- end stage renal disease
- endothelial cells
- rheumatoid arthritis
- newly diagnosed
- ejection fraction
- chronic kidney disease
- prognostic factors
- poor prognosis
- circulating tumor cells
- machine learning
- randomized controlled trial
- drug delivery
- big data
- induced pluripotent stem cells
- transcription factor
- electronic health record
- data analysis
- systematic review
- free survival
- smoking cessation
- genome wide identification