PMID- 18094376
OWN - NLM
STAT- MEDLINE
DCOM- 20071227
LR  - 20220410
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Print)
IS  - 0028-4793 (Linking)
VI  - 357
IP  - 25
DP  - 2007 Dec 20
TI  - TP53 mutations and survival in squamous-cell carcinoma of the head and neck.
PG  - 2552-61
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.
CI  - Copyright 2007 Massachusetts Medical Society.
FAU - Poeta, M Luana
AU  - Poeta ML
AD  - Johns Hopkins University, Baltimore, MD 21287, USA.
FAU - Manola, Judith
AU  - Manola J
FAU - Goldwasser, Meredith A
AU  - Goldwasser MA
FAU - Forastiere, Arlene
AU  - Forastiere A
FAU - Benoit, Nicole
AU  - Benoit N
FAU - Califano, Joseph A
AU  - Califano JA
FAU - Ridge, John A
AU  - Ridge JA
FAU - Goodwin, Jarrard
AU  - Goodwin J
FAU - Kenady, Daniel
AU  - Kenady D
FAU - Saunders, John
AU  - Saunders J
FAU - Westra, William
AU  - Westra W
FAU - Sidransky, David
AU  - Sidransky D
FAU - Koch, Wayne M
AU  - Koch WM
LA  - eng
GR  - R01 DE013152/DE/NIDCR NIH HHS/United States
GR  - R01 DE013152-09/DE/NIDCR NIH HHS/United States
GR  - U10 CA023318/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
CIN - N Engl J Med. 2007 Dec 20;357(25):2539-41. PMID: 18094374
CIN - N Engl J Med. 2008 Mar 13;358(11):1194; author reply 1195. PMID: 18337610
CIN - N Engl J Med. 2008 Mar 13;358(11):1194-5; author reply 1195. PMID: 18340660
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Squamous Cell/*genetics/mortality/pathology/surgery
MH  - DNA Mutational Analysis
MH  - *DNA, Neoplasm/analysis
MH  - Female
MH  - *Genes, p53
MH  - Head and Neck Neoplasms/*genetics/mortality/pathology/surgery
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - *Mutation
MH  - Neoplasm Staging
MH  - Oligonucleotide Array Sequence Analysis
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Prospective Studies
MH  - Tumor Suppressor Protein p53/*genetics
PMC - PMC2263014
MID - NIHMS41131
COIS- No potential conflict of interest relevant to this article was reported.
EDAT- 2007/12/21 09:00
MHDA- 2007/12/29 09:00
PMCR- 2008/03/05
CRDT- 2007/12/21 09:00
PHST- 2007/12/21 09:00 [pubmed]
PHST- 2007/12/29 09:00 [medline]
PHST- 2007/12/21 09:00 [entrez]
PHST- 2008/03/05 00:00 [pmc-release]
AID - 357/25/2552 [pii]
AID - 10.1056/NEJMoa073770 [doi]
PST - ppublish
SO  - N Engl J Med. 2007 Dec 20;357(25):2552-61. doi: 10.1056/NEJMoa073770.