PMID- 10092071
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20051117
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 79
IP  - 3
DP  - 1999 Mar
TI  - Sequencing analysis of RNA and DNA of exons 1 through 11 shows p53 gene
      alterations to be present in almost 100% of head and neck squamous cell cancers.
PG  - 347-53
AB  - Data on p53 alterations in human cancers are mainly based on studies restricted
      to the core domain (exons 5-9), because mutations outside this region are assumed
      to be rare. To test this assumption, we studied 25 consecutive patients with
      primary, untreated head and neck squamous cell carcinoma (HNSCC) with a p53
      mutation analysis strategy that consists of sequencing all 11 p53 exons and the
      complete p53 mRNA. With this method, we encountered p53 mutations in 91% of
      patients; 33% of these were located outside the core domain. Overexpression of
      the p53 protein was assessed with staining with antibody Bp 53-12-1. Protein
      overexpression was found in 64%. In one case, p53 overexpression occurred without
      p53 gene mutations. Analysis of tumor tissue from two autopsied patients with
      multiple lesions in the head and neck and at distant sites allowed analysis of
      the clonal relationship of the different tumor foci. In one patient, the head and
      neck lesion had a mutation different from the one observed at the distant sites, 
      suggesting two different primary tumors, one of them leading to widespread
      metastastic disease. In all lesions from the second patient, the same mutation
      was found, suggesting one primary that had metastatized. It appears that
      sequencing of all exons of the p53 gene is vital for assessment of the real
      incidence of p53 mutations in HNSCC, because 33% of all mutations are located
      outside the core domain, leading to a mutation frequency of almost 100% in HNSCC.
      In 96% of cases, either presence or absence of p53 protein expression could be
      explained by the type of p53 gene mutation. When only analyzing the p53 core
      domain, the incidence of p53 mutations in HNSCC is underestimated.
FAU - Kropveld, A
AU  - Kropveld A
AD  - Department of Otorhinolaryngology, University Hospital Utrecht, The Netherlands.
FAU - Rozemuller, E H
AU  - Rozemuller EH
FAU - Leppers, F G
AU  - Leppers FG
FAU - Scheidel, K C
AU  - Scheidel KC
FAU - de Weger, R A
AU  - de Weger RA
FAU - Koole, R
AU  - Koole R
FAU - Hordijk, G J
AU  - Hordijk GJ
FAU - Slootweg, P J
AU  - Slootweg PJ
FAU - Tilanus, M G
AU  - Tilanus MG
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (DNA, Neoplasm)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Amino Acid Sequence/genetics
MH  - Base Sequence/genetics
MH  - Cadaver
MH  - Carcinoma, Squamous Cell/*genetics/metabolism
MH  - DNA, Neoplasm/genetics
MH  - Exons/*genetics
MH  - Female
MH  - Head and Neck Neoplasms/*genetics/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Mutation/*genetics
MH  - Point Mutation/genetics
MH  - RNA, Neoplasm/genetics
MH  - Tumor Suppressor Protein p53/*genetics/metabolism
EDAT- 1999/03/26 00:00
MHDA- 1999/03/26 00:01
CRDT- 1999/03/26 00:00
PHST- 1999/03/26 00:00 [pubmed]
PHST- 1999/03/26 00:01 [medline]
PHST- 1999/03/26 00:00 [entrez]
PST - ppublish
SO  - Lab Invest. 1999 Mar;79(3):347-53.