In an analysis of molecular and clinical features associated with survival in head and neck squamous cell carcinoma reported in Nature Genetics, Gross and colleagues found that the TP53 mutation is frequently accompanied by loss of chromosome 3p; the combination of these alterations was associated with median overall survival of 1.9 years, compared with > 5 years in patients with the TP53 mutation alone. The interaction with TP53 was found to be specific to chromosome 3p and was identified in head and neck cancer and other cancer cohorts.
Human papillomavirus (HPV) inactivates TP53, and chromosome 3p deletion was found to be common and associated with poor outcome in HPV-positive head and neck tumors. The TP53-3p interaction was found to be modified by microRNA548k expression; this modification was associated with a further reduction in survival and was found to occur mutually exclusively with mutations affecting RAS signaling.
The investigators concluded, “Together, the identified markers underscore the molecular heterogeneity of [head and neck squamous cell carcinoma] and enable a new multi-tiered classification of this disease.” ■
Gross AM, et al: Nat Genet. August 3, 2014 (early release online).