Investigations on a clinically and functionally unusual and novel germline p53 mutation
| Autor: | Graham R. Taylor, Ruth Charlton, Diana M. Barnes, Richard Camplejohn, Xin Lu, C E Chu, P M Duddy, J Rutherford, P Chumas |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
p53
Cancer Research DNA Mutational Analysis Apoptosis medicine.disease_cause Germline Exon Mutant protein Tumor Cells Cultured Lymphocytes Frameshift Mutation Tumor Stem Cell Assay Osteosarcoma Mutation Li Fraumeni Neoplasms Second Primary DNA Neoplasm Exons Neoplasm Proteins Pedigree Oncology Codon Nonsense Female Choroid plexus Adult Transcriptional Activation Choroid Plexus Neoplasms Recombinant Fusion Proteins Molecular Sequence Data Bone Neoplasms Saccharomyces cerevisiae Biology Transfection Frameshift mutation Germline mutation medicine Humans Genetic Predisposition to Disease Gene Alleles Germ-Line Mutation choroid plexus Base Sequence Papilloma Genetics and Genomics Genes p53 Molecular biology Mutagenesis Insertional Amino Acid Substitution Cancer research Tumor Suppressor Protein p53 |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6600269 |
| Popis: | This report describes an individual with a rare choroid plexus papilloma in adulthood (age 29) after earlier having an osteosarcoma (age 22). The results from this study, and others, suggest that it may be advisable to consider the possibility of a germline p53 mutation in adults presenting with choroid plexus tumours. In the current study automated DNA sequencing of genomic DNA detected a novel germline 7 base pair insertion in exon 5 of the p53 gene in this patient. The alteration in frame would produce amino acid substitutions beginning with alanine to glycine at position 161 and a stop codon at position 182 in the mutated protein. Surprisingly two assays of p53 function gave apparently wild-type results on peripheral blood lymphocytes from this individual. These results led us to carry out more detailed functional tests on the mutant protein. The mutant allele was expressed either at very low levels or not at all in phytohaemagglutinin stimulated lymphocytes. Further, the mutant protein was completely non-functional in terms of its ability to transactivate a series of p53-responsive genes (p21WAF1, bax, PIG3), to transrepress a target gene and to inhibit colony growth in transfected Saos-2 cells. However, surprisingly, data from irradiated peripheral blood lymphocytes and transfected Saos-2 cells, suggested that this truncated, mutant protein retains significant ability to induce apoptosis. British Journal of Cancer (2002) 86, 1592–1596. DOI: 10.1038/sj/bjc/6600269 www.bjcancer.com © 2002 Cancer Research UK |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|