Field cancerisation and polyclonal p53 mutation in the upper aero-digestive tract
Details
Serval ID
serval:BIB_DD224BCB91A7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Field cancerisation and polyclonal p53 mutation in the upper aero-digestive tract
Journal
Oncogene
ISSN
0950-9232 (Print)
Publication state
Published
Issued date
01/1997
Volume
14
Number
2
Pages
163-9
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan 16
Research Support, Non-U.S. Gov't --- Old month value: Jan 16
Abstract
Field cancerisation of the aerodigestive tract is caused by chronic exposure to alcohol and tobacco, but the nature of the genetic alterations preceding overt malignancy is unknown. To identify potential field changes we have used a functional assay which tests the transcriptional competence of human p53 expressed in yeast. To increase the sensitivity and reliability of the technique for samples containing under 20% mutant p53, the 5' and 3'-ends of the p53 cDNA were examined separately. With this split form of the assay the tissue p53 mRNA acts as its own control for RNA quality. Mutations were detected in 87% (46/53) of tumours, reflecting the high sensitivity of the technique. Multiple biopsies of histologically normal tissue from the upper aero-digestive tract were tested and clonal p53 mutations were identified in 76% (38/50) of biopsies from patients presenting with multiple tumours compared with 32% (38/117) of biopsies from patients presenting with single tumours (P<0.000001). All patients (16/16) presenting with multiple tumours had at least one positive biopsy, compared with only 53% (19/36) of patients presenting with single tumours (P <0.001). This defines expansion of multiple clones of mutant p53-containing cells as an important biological mechanism of field cancerisation, and provides a means to identify patients likely to benefit from intensive screening for the development of new head and neck tumours.
Keywords
Adult
Aged
Carcinoma, Squamous Cell/chemistry/*genetics
Female
Gene Expression Regulation, Neoplastic
Genes, p53/*genetics
Genetic Vectors
Head and Neck Neoplasms/chemistry/*genetics
Humans
Male
Middle Aged
Neoplasms, Multiple Primary/genetics/metabolism
Precancerous Conditions/chemistry/*genetics
RNA, Messenger/*analysis
Sensitivity and Specificity
*Sequence Deletion
Tumor Suppressor Protein p53/*analysis/genetics
Yeasts/genetics
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 10:58
Last modification date
20/08/2019 16:01