The relationship between allelic imbalance on 17p, p53 mutation and p53 overexpression in head and neck cancer.
The huge majority of head and neck squamous cell carcinoma (HNSCC) show alterations of p53 either on the genetic level or on the protein level. Allelic imbalance (AI)/loss of heterozygosity (LOH) on 17p at the p53 locus is frequent in HNSCC. However, the complex relationship between these phenomena is poorly understood in HNSCC. We investigated one group of 39 HNSCC for: a) allelic imbalance on 17p using 4 microsatellite markers located throughout this chromosomal arm; b) mutations of p53 in exons 5-9; and c) overexpression of p53 using two antibodies located on opposite ends of the protein. AI/LOH was detected in 44% at the locus TP53, rising to 69% when regarding all 4 markers on 17p. Therefore, our data are in line with the assumption of additional tumour suppressor genes on 17p in HNSCC. A nuclear accumulation of p53 (51%) was independent from the antibody and the recognised epitope. At the first glance there was no correlation between overall p53 mutation (36%) and overexpression. However, it appeared that, with very few exceptions, only nonsense mutations did not lead to p53 overexpression, while missense mutations did. As overexpression of p53 was 15% more frequent than p53 mutations and only 35% of the tumours with p53 overexpression carried a p53 mutation, our data support the hypothesis of additional mechanisms of p53 overexpression. AI/LOH at the p53 locus in 83% of all tumours with a p53 mutation is in line with Knudson's theory of inactivation of tumour suppressor genes.
Götte
K
K
Research Laboratory, Department of Otolaryngology, Head and Neck Surgery, University Hospital Mannheim, D-68135 Mannheim, Germany. karl.goette@hno.ma.uni-heidelberg.de
Riedel
F
F
Neubauer
J
J
Schäfer
C
C
Coy
J F
JF
Hörmann
K
K
D022981:Allelic Imbalance; D001483:Base Sequence; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53