Sequential p53 mutation analysis of pre‐invasive and invasive head and neck squamous carcinoma

Abstract

Single-stranded conformational polymorphism (SSCP) and direct sequencing were performed on uninvolved mucosa, severe dysplasia and invasive carcinoma samples from 20 patients with head and neck squamous carcinoma. Seven (35%) of the non-invasive lesions and 15 (75%) of the invasive carcinomas manifested p53 mutations. Although the majority of mutations were mis-sense, resulting in single amino acid substitution, a silent mutation encoding for the same amino acid and 2 non-sense mutations encoding a stop codon were also observed. Mutations in invasive carcinoma were mostly in exon 8 and involved codons 296, 288 and 298; non-invasive lesions showed more mutations at exons 5 to 7. Five lesions showed simultaneous mutations in 2 different exons; in 3 both non-invasive and invasive carcinomas showed primary mutation at exons 5 to 7, and invasive carcinoma showed a secondary mutation at exon 8. Different codon mutations in the same exon between dysplastic and the corresponding carcinoma samples were found in 2 cases. p53 alterations were not observed in any of the normal mucosa samples. No apparent association between p53 mutations and conventional clinicopathologic parameters, including DNA content, was found in this cohort. Our study indicates that (i) p53 alteration is an early event in the genesis of a subset of head and neck squamous carcinomas, (ii) normal mucosa within the resected specimens lacked p53 mutation, (iii) sequential mutations of different exons of the p53 gene suggests accumulation of genetic alterations during the neoplastic transformation of these lesions and (iv) the difference in codon mutation of the same exon between dysplastic and corresponding carcinoma suggests an independent clonal development.

Genomic alterations in nasopharyngeal carcinoma: loss of heterozygosity and Epstein-Barr virus infection

“…It would be of great interest and importance to elucidate whether the genetic events in Epstein-Barr virus-associated NPC are similar or distinct from HNSCC. Previous HNSCC studies have demonstrated a high frequency of LOH on chromosomes 3p, 3q, 6p, 8p, 8q, 9p, 1 lq, 13q, 14q, 17p, 18q and 19q (Nawroz et al, 1994;El-Naggar et al, 1995;Field et al, 1995). Nawroz et al (1994) studied 29 HNSCCs and showed 67, 50, 38, 40, 38, 72, 61, 54, 39, 52, 23 and 40% allelic losses respectively.…”

“…The aim of this study was to investigate whether other tumour-suppressor genes are also involved in NPC development by analysing the loss of heterozygosity (LOH) on every autosomal arm. Interestingly, allelotyping of HNSCC have been well characterized (Nawroz et al, 1994;El-Naggar et al, 1995;Field et al, 1995). Allelic loss on chromosome 3p, 9p and 1 lq are also frequent events in HNSCC.…”

“…In addition, frequent LOH was observed on other chromosomes, e.g. 6p, 8, 13q, 14q, 17p, 18q and 19q (Nawroz et al, 1994;El-Naggar et al, 1995;Field et al, 1995). It would be of great interest and importance to elucidate whether the genetic events in Epstein-Barr virus-associated NPC are similar or distinct from HNSCC.…”

High incidence of loss of heterozygosity at chromosome 17p13 in breast tumours from BRCA2 mutation carriers

“…The PCR ampli®cation and SSCP conditions for exons 5 ± 9 are described by El-Naggar et al (1995), and for exon 4 by Deng et al (1994). PCR products were diluted 1 : 4 in 95% formamide, 10 mM NaOH, 0.025% xylene cyanol and 0.025% bromophenol blue and denatured at 958C for 8 ± 10 min.…”

Telomerase Activity Is Upregulated in Laryngeal Squamous Cell Carcinoma

“…To date, numerous genetic changes have been elucidated, but none have been found to be exclusively associated with malignancy. 2,3 One factor that appears to be present in all cancer cells is the active form of the ribonucleoprotein enzyme, telomerase. 4 The finding that telomerase activity is completely absent or present at low levels in normal somatic tissue, except germ-line cells, and present at high levels in most human carcinomas studied to date, has led to attempts at targeting the enzyme as a molecular marker.…”