PUMA in head and neck cancer.

Abstract

Genetic alterations of p53, which monitors DNA damage and operates cellular checkpoints, is a major factor in the development of many types of cancer in human. PUMA, a direct mediator of p53-associated apoptosis, was recently identified. The PUMA gene was mapped to chromosomal arm 19q, a region frequently deleted in head/neck and lung cancers. We analyzed 30 primary tumors (15 head/neck and 15 lung) for loss of heterozygosity (LOH) at 19q using seven widely spaced microsatellite markers. LOH in at least one marker was present in 8 (56%) of the head/neck and 4 (26.6%) of the lung cancer samples. Overall, D19S408 and D19S412, showed the highest rates of allelic loss (23.3 and 16.6%, respectively). We then sequenced the entire coding region of the PUMA gene in all the 30 primary tumors and in 10 head/neck cancer cell lines. No mutations of PUMA were detected in any samples examined, regardless of the mutational status of the p53 gene. Forced expression of wild-type PUMA in JHU-012 and JHU-013 head/neck cancer cell lines significantly inhibited colony formation. Although PUMA suppresses tumor cell growth in head/neck cancer, it does not appear to be a direct target of inactivation in head and neck tumorigenesis.