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

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

Research output: Contribution to journalArticle

423 Citations (Scopus)

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<0.001) and no significant association with nondisruptive mutations (hazard ratio, 1.2; 95% CI, 0.9 to 1.7; P = 0.16). In multivariate analyses a disruptive TP53 alteration, as compared with the absence of a TP53 mutation, had an independent, significant association with decreased survival (hazard ratio, 1.7; 95% CI, 1.2 to 2.4; P = 0.003). CONCLUSIONS: Disruptive TP53 mutations in tumor DNA are associated with reduced survival after surgical treatment of squamous-cell carcinoma of the head and neck.

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

Fingerprint

Mutation
Survival
Confidence Intervals
DNA
Neoplasms
Carcinoma, squamous cell of head and neck
Tumor Suppressor Protein p53
Deoxyribonuclease I
p53 Genes
Multivariate Analysis
High Pressure Liquid Chromatography
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Poeta, M. L., Manola, J., Goldwasser, M. A., Forastiere, A., Benoit, N., Califano, J. A., ... Koch, W. M. (2007). TP53 mutations and survival in squamous-cell carcinoma of the head and neck. New England Journal of Medicine, 357(25), 2552-2561. https://doi.org/10.1056/NEJMoa073770

TP53 mutations and survival in squamous-cell carcinoma of the head and neck. / Poeta, M. Luana; Manola, Judith; Goldwasser, Meredith A.; Forastiere, Arlene; Benoit, Nicole; Califano, Joseph A.; Ridge, John A.; Goodwin, W. Jarrard; Kenady, Daniel; Saunders, John; Westra, William; Sidransky, David; Koch, Wayne M.

In: New England Journal of Medicine, Vol. 357, No. 25, 20.12.2007, p. 2552-2561.

Research output: Contribution to journalArticle

Poeta, ML, Manola, J, Goldwasser, MA, Forastiere, A, Benoit, N, Califano, JA, Ridge, JA, Goodwin, WJ, Kenady, D, Saunders, J, Westra, W, Sidransky, D & Koch, WM 2007, 'TP53 mutations and survival in squamous-cell carcinoma of the head and neck', New England Journal of Medicine, vol. 357, no. 25, pp. 2552-2561. https://doi.org/10.1056/NEJMoa073770
Poeta ML, Manola J, Goldwasser MA, Forastiere A, Benoit N, Califano JA et al. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. New England Journal of Medicine. 2007 Dec 20;357(25):2552-2561. https://doi.org/10.1056/NEJMoa073770
Poeta, M. Luana ; Manola, Judith ; Goldwasser, Meredith A. ; Forastiere, Arlene ; Benoit, Nicole ; Califano, Joseph A. ; Ridge, John A. ; Goodwin, W. Jarrard ; Kenady, Daniel ; Saunders, John ; Westra, William ; Sidransky, David ; Koch, Wayne M. / TP53 mutations and survival in squamous-cell carcinoma of the head and neck. In: New England Journal of Medicine. 2007 ; Vol. 357, No. 25. pp. 2552-2561.
@article{09f2c6b3504d4de5979f99764ee3b4bc,
title = "TP53 mutations and survival in squamous-cell carcinoma of the head and neck",
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<0.001) and no significant association with nondisruptive mutations (hazard ratio, 1.2; 95{\%} CI, 0.9 to 1.7; P = 0.16). In multivariate analyses a disruptive TP53 alteration, as compared with the absence of a TP53 mutation, had an independent, significant association with decreased survival (hazard ratio, 1.7; 95{\%} CI, 1.2 to 2.4; P = 0.003). CONCLUSIONS: Disruptive TP53 mutations in tumor DNA are associated with reduced survival after surgical treatment of squamous-cell carcinoma of the head and neck.",
author = "Poeta, {M. Luana} and Judith Manola and Goldwasser, {Meredith A.} and Arlene Forastiere and Nicole Benoit and Califano, {Joseph A.} and Ridge, {John A.} and Goodwin, {W. Jarrard} and Daniel Kenady and John Saunders and William Westra and David Sidransky and Koch, {Wayne M.}",
year = "2007",
month = "12",
day = "20",
doi = "10.1056/NEJMoa073770",
language = "English",
volume = "357",
pages = "2552--2561",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "25",

}

TY - JOUR

T1 - TP53 mutations and survival in squamous-cell carcinoma of the head and neck

AU - Poeta, M. Luana

AU - Manola, Judith

AU - Goldwasser, Meredith A.

AU - Forastiere, Arlene

AU - Benoit, Nicole

AU - Califano, Joseph A.

AU - Ridge, John A.

AU - Goodwin, W. Jarrard

AU - Kenady, Daniel

AU - Saunders, John

AU - Westra, William

AU - Sidransky, David

AU - Koch, Wayne M.

PY - 2007/12/20

Y1 - 2007/12/20

N2 - 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<0.001) and no significant association with nondisruptive mutations (hazard ratio, 1.2; 95% CI, 0.9 to 1.7; P = 0.16). In multivariate analyses a disruptive TP53 alteration, as compared with the absence of a TP53 mutation, had an independent, significant association with decreased survival (hazard ratio, 1.7; 95% CI, 1.2 to 2.4; P = 0.003). CONCLUSIONS: Disruptive TP53 mutations in tumor DNA are associated with reduced survival after surgical treatment of squamous-cell carcinoma of the head and neck.

AB - 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<0.001) and no significant association with nondisruptive mutations (hazard ratio, 1.2; 95% CI, 0.9 to 1.7; P = 0.16). In multivariate analyses a disruptive TP53 alteration, as compared with the absence of a TP53 mutation, had an independent, significant association with decreased survival (hazard ratio, 1.7; 95% CI, 1.2 to 2.4; P = 0.003). CONCLUSIONS: Disruptive TP53 mutations in tumor DNA are associated with reduced survival after surgical treatment of squamous-cell carcinoma of the head and neck.

UR - http://www.scopus.com/inward/record.url?scp=37349055876&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37349055876&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa073770

DO - 10.1056/NEJMoa073770

M3 - Article

C2 - 18094376

AN - SCOPUS:37349055876

VL - 357

SP - 2552

EP - 2561

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 25

ER -