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NCI CANCERLIT^® Search: Li-Fraumeni Syndrome - July 2002

National Cancer Institute^®
Last Modified: July 1, 2002

A novel, de novo germline TP53 mutation in a rare presentation of the Li-Fraumeni syndrome in the maxilla.
Comment on: S.S. Prime et al. "A review of inherited cancer syndromes and their relevance to oral squamous cell carcinoma" Oral Oncology
Assessing TP53 status in human tumours to evaluate clinical outcome.
RNA polymerase III transcription can be derepressed by oncogenes or mutations that compromise p53 function in tumours and Li-Fraumeni

Table of Contents

1
UI - 12076704
AU - Patrikidou A; Bennett J; Abou-Sleiman P; Delhanty JD; Harris M
TI - A novel, de novo germline TP53 mutation in a rare presentation of the Li-Fraumeni syndrome in the maxilla.
SO - Oral Oncol 2002 Jun;38(4):383-90
AD - Department of Oral and Maxillofacial Surgery, Eastman Dental Institute for Oral Health Care Sciences, University College London, 256 Gray's Inn Road, London WC1X 8LD, UK. a.patrikidou@eastman.ucl.ac.uk
We undertook the genetic analysis of a classic Li-Fraumeni syndrome (LFS) family with clustering of primary tumours including two maxillary sarcomas, a rare LFS site of tumour occurrence. Our aim was to investigate the presence of a specific type of TP53 mutation that could be associated with this unusual predilection of site for cancer occurrence. Mutational screening of the coding region of TP53 revealed an A>T transversion in codon 144 of exon 5 (CAG>CTG, Gln>Leu) in the germline of one of the three affected members, with loss of heterozygosity (LOH) in the tumour tissue. All other affected members were negative for germline or somatic TP53 mutations. TP53 immunohistochemistry was uninformative. The mutation we report is a de novo constitutional TP53 mutation that has not been previously described in the literature. It could explain the more burdened phenotype of the affected patient (died at 21 months). Alternative mechanisms to explain the overall family phenotype are discussed.

2
UI - 11854072
AU - Patrikidou A; Harris M; Bennett J; Abou-Sleiman P; Delhanty JD
TI - Comment on: S.S. Prime et al. "A review of inherited cancer syndromes and their relevance to oral squamous cell carcinoma" Oral Oncology 2001;37(1), 1-16.
SO - Oral Oncol 2002 Feb;38(2):216-7

3
UI - 11902578
AU - Soussi T; Beroud C
TI - Assessing TP53 status in human tumours to evaluate clinical outcome.
SO - Nat Rev Cancer 2001 Dec;1(3):233-40
AD - Institut Curie, Universite P. & M. Curie, Laboratoire de Genotoxicologie des Tumeurs, Paris, France. thierry.soussi@curie.fr
TP53 is probably the most extensively studied tumour-suppressor gene, and patients with TP53 mutations are known to have a poor outcome. However, inconsistencies in the analysis of TP53 status, and failure to realize that different mutations behave in different ways, prevent us from effectively applying our vast knowledge of this protein in clinical practice. What simple steps can be taken to ensure that patients benefit from our understanding of TP53?

4
UI - 12082526
AU - Stein T; Crighton D; Boyle JM; Varley JM; White RJ
TI - RNA polymerase III transcription can be derepressed by oncogenes or mutations that compromise p53 function in tumours and Li-Fraumeni syndrome.
SO - Oncogene 2002 May 2;21(19):2961-70
AD - Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, Glasgow G12 8QQ, Scotland, UK.
RNA polymerase (pol) III synthesizes essential small RNAs, including tRNA and 5S rRNA. Wild-type p53 can repress pol III transcription both in vitro and in vivo. Many tumours carry substitutions in p53 which have selective effects on its functions. We identify tumour-derived mutations that compromise the ability of p53 to regulate pol III transcription. Furthermore, substitution R175H, the most common mutation in cancers, converts p53 from a repressor to an activator of pol III. Oncoproteins neutralize p53 in some tumours; we show that human papillomavirus E6 and cellular hdm2 can both release pol III from repression by p53. These data suggest that the restraining influence of p53 on pol III will be lost in many tumours. In addition to these features of sporadic cancers, some individuals inherit mutant forms of p53 and consequently suffer from Li-Fraumeni syndrome, showing genetic predisposition to certain malignancies. We find that pol III transcriptional activity is often highly elevated in primary fibroblasts from Li-Fraumeni patients, especially if the germline p53 mutation is followed by loss of the remaining allele. Our data suggest that p53 status can have a profound effect upon pol III transcription and hence on the biosynthetic capacity of cells.

The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.

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