Sequencing analysis of RNA and DNA of exons 1 through 11 shows p53 gene alterations to be present in almost 100% of head and neck squamous cell cancers
A. Kropveld et al., Sequencing analysis of RNA and DNA of exons 1 through 11 shows p53 gene alterations to be present in almost 100% of head and neck squamous cell cancers, LAB INV, 79(3), 1999, pp. 347-353
Data on p53 alterations in human cancers are mainly based on studies restri
cted to the core domain (exons 5-9), because mutations outside this region
are assumed to be rare. To test this assumption, we studied 25 consecutive
patients with primary, untreated head and neck squamous cell carcinoma (HNS
CC) with a p53 mutation analysis strategy that consists of sequencing all 1
1 p53 exons and the complete p53 mRNA. With this method, we encountered p53
mutations in 91% of patients; 33% of these were located outside the core d
omain. Overexpression of the p53 protein was assessed with staining with an
tibody Bp 53-12-1. Protein overexpression was found in 64%. In one case, p5
3 overexpression occurred without p53 gene mutations. Analysis of tumor tis
sue from two autopsied patients with multiple lesions in the head and neck
and at distant sites allowed analysis of the clonal relationship of the dif
ferent tumor foci. In one patient, the head and neck lesion had a mutation
different from the one observed at the distant sites, suggesting two differ
ent primary tumors, one of them leading to widespread metastastic disease.
In all lesions from the second patient, the same mutation was found, sugges
ting one primary that had metastatized. It appears that sequencing of all e
xons of the p53 gene is vital for assessment of the real incidence of p53 m
utations in HNSCC, because 33% of all mutations are located outside the cor
e domain, leading to a mutation frequency of almost 100% in HNSCC. In 96% o
f cases, either presence or absence of p53 protein expression could be expl
ained by the type of p53 gene mutation. When only analyzing the p53 core do
main, the incidence of p53 mutations in HNSCC is underestimated.