TP53 mutations and survival in squamous-cell carcinoma of the head and neck

M. Luana Poeta, Judith Manola, Meredith A. Goldwasser, Arlene A. Forastiere, Nicole Benoit, Joseph A. Califano, John A. Ridge, Jarrard Goodwin, Daniel Kenady, John Saunders, William Westra, David Sidransky, Wayne Martin Koch

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Abstract

BACKGROUND: The abrogation of function of the tumor-suppressor protein p53 as a result of mutation of its gene, TP53, is one of the most common genetic alterations in cancer cells. We evaluated TP53 mutations and survival in patients with squamous-cell carcinoma of the head and neck. METHODS: A total of 560 patients with squamous-cell carcinoma of the head and neck who were treated surgically with curative intent were enrolled in our prospective multicenter, 7-year study. TP53 mutations were analyzed in DNA from the tumor specimens with the use of the Affymetrix p53 chip and the Surveyor DNA endonuclease and denaturing high-performance liquid chromatography. Mutations were classified into two groups, disruptive and nondisruptive, according to the degree of disturbance of protein structure predicted from the crystal structure of the p53-DNA complexes. TP53 mutational status was compared with clinical outcome. RESULTS: TP53 mutations were found in tumors from 224 of 420 patients (53.3%). As compared with wild-type TP53, the presence of any TP53 mutation was associated with decreased overall survival (hazard ratio for death, 1.4; 95% confidence interval [CI], 1.1 to 1.8; P = 0.009), with an even stronger association with disruptive mutations (hazard ratio, 1.7; 95% CI, 1.3 to 2.4; P

Original languageEnglish (US)
Pages (from-to)2552-2561
Number of pages10
JournalNew England Journal of Medicine
Volume357
Issue number25
DOIs
Publication statusPublished - Dec 20 2007

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ASJC Scopus subject areas

  • Medicine(all)

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