PUMA in head and neck cancer

Cancer Lett. 2003 Sep 10;199(1):75-81. doi: 10.1016/s0304-3835(03)00344-6.

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.

MeSH terms

  • Apoptosis Regulatory Proteins
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 19*
  • DNA Damage
  • DNA Primers
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Loss of Heterozygosity
  • Lung Neoplasms / genetics
  • Microsatellite Repeats
  • Molecular Sequence Data
  • Neoplasms / genetics*
  • Proteins / genetics*
  • Proto-Oncogene Proteins*
  • Tumor Suppressor Protein p53*

Substances

  • Apoptosis Regulatory Proteins
  • BBC3 protein, human
  • DNA Primers
  • Proteins
  • Proto-Oncogene Proteins
  • Tumor Suppressor Protein p53