PUMA in head and neck cancer.
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.
Hoque
Mohammad Obaidul
MO
Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins School of Medicine, Ross Research Building, Room 818, 720 Rutland Avenue, Baltimore, MD 21205-2196, USA.
Begum
Shahnaz
S
Sommer
Matthias
M
Lee
Taekyeol
T
Trink
Barry
B
Ratovitski
Edward
E
Sidransky
David
D
D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D004249:DNA Damage; D017931:DNA Primers; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D017931:DNA Primers; D011506:Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53