title: Genome-Wide Loss of Heterozygosity and DNA Copy Number Aberration in HPV-Negative Oral Squamous Cell Carcinoma and Their Associations with Disease-Specific Survival.
abstract: Oral squamous cell cancer of the oral cavity and oropharynx (OSCC) is associated with high case-fatality. For reasons that are largely unknown, patients with the same clinical and pathologic staging have heterogeneous response to treatment and different probability of recurrence and survival, with patients with Human Papillomavirus (HPV)-positive oropharyngeal tumors having the most favorable survival. To gain insight into the complexity of OSCC and to identify potential chromosomal changes that may be associated with OSCC mortality, we used Affymtrix 6.0 SNP arrays to examine paired DNA from peripheral blood and tumor cell populations isolated by laser capture microdissection to assess genome-wide loss of heterozygosity (LOH) and DNA copy number aberration (CNA) and their associations with risk factors, tumor characteristics, and oral cancer-specific mortality among 75 patients with HPV-negative OSCC. We found a highly heterogeneous and complex genomic landscape of HPV-negative tumors, and identified regions in 4q, 8p, 9p and 11q that seem to play an important role in oral cancer biology and survival from this disease. If confirmed, these findings could assist in designing personalized treatment or in the creation of models to predict survival in patients with HPV-negative OSCC.
authors.affiliation: Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington, United States of America; Department of Epidemiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Program in Biostatistics and Biomathematics, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Yuzheng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Loomis
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Upton
authors.affiliation: Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Pawadee
authors.initials: P
authors.lastname: Lohavanichbutr
authors.affiliation: Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: John R
authors.initials: JR
authors.lastname: Houck
authors.affiliation: Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: David R
authors.initials: DR
authors.lastname: Doody
authors.affiliation: Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington, United States of America; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mendez
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington, United States of America.
authors.forename: Neal
authors.initials: N
authors.lastname: Futran
authors.affiliation: Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Department of Epidemiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Schwartz
authors.affiliation: Program in Biostatistics and Biomathematics, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Department of Genetics and Genomics Sciences, Mt. Sinai School of Medicine, New York, New York, United States of America.
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002877:Chromosomes, Human; D056915:DNA Copy Number Variations; D056426:Genetic Loci; D015894:Genome, Human; D006801:Humans; D007830:Larynx / Q000378:metabolism / Q000473:pathology; D061346:Laser Capture Microdissection; D019656:Loss of Heterozygosity; D009055:Mouth / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D027383:Papillomaviridae; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis