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Sequential p53 mutation analysis of pre‐invasive and invasive head and neck squamous carcinoma
Author(s) -
ElNaggar Adel K.,
Lai Syeling,
Luna Mario A.,
Zhou XiaoDong,
Weber Randal S.,
Goepfert Helmuth,
Batsakis John G.
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910640309
Subject(s) - exon , mutation , biology , silent mutation , single strand conformation polymorphism , pathology , carcinoma , point mutation , epidermoid carcinoma , squamous carcinoma , head and neck squamous cell carcinoma , cancer research , gene , microbiology and biotechnology , genetics , head and neck cancer , cancer , missense mutation , medicine
Single‐stranded conformation 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 p 53 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. p 53 alterations were not observed in any of the normal mucosa samples. No apparent association between p 53 mutations and conventional clinicopathologic parameters, including DNA content, was found in this cohort. Our study indicates that (i) p 53 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 p 53 mutation, (iii) sequential mutations of different exons of the p 53 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. © 1995 Wiley‐Liss, Inc.