A constitutional de novo mutation in exon 8 of the p53 gene in a patient with multiple primary malignancies.

We report a constitutional point mutation of codon 278 in exon 8 of the TP53 gene that has not yet been described as a germ-line mutation. A 52-year-old female developed multiple primary malignancies (liposarcoma, breast cancer, malignant histiocytoma, occult adenocarcinoma). The mutation found in h...

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Main Authors:	Speiser, P., Gharehbaghi-Schnell, E., Eder, S., Haid, A., Kovarík, J., Nenutil, R., Sauter, G., Schneeberger, C. H., Vojtesek, B., Wiltschke, C. H., Zeillinger, R.
Format:	Online
Language:	English
Published:	Nature Publishing Group 1996
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074589/

id	pubmed-2074589
recordtype	oai_dc
spelling	pubmed-20745892009-09-10 A constitutional de novo mutation in exon 8 of the p53 gene in a patient with multiple primary malignancies. Speiser, P. Gharehbaghi-Schnell, E. Eder, S. Haid, A. Kovarík, J. Nenutil, R. Sauter, G. Schneeberger, C. H. Vojtesek, B. Wiltschke, C. H. Zeillinger, R. Research Article We report a constitutional point mutation of codon 278 in exon 8 of the TP53 gene that has not yet been described as a germ-line mutation. A 52-year-old female developed multiple primary malignancies (liposarcoma, breast cancer, malignant histiocytoma, occult adenocarcinoma). The mutation found in her tumour and peripheral blood lymphocyte DNA is a cytosine to thymine transition at the second position of codon 278 resulting in an amino acid exchange from proline to leucine in the DNA-binding domain. Evaluation of the patient's family revealed that both of her sons were affected by the same mutation. Although the patient's mother had died already, we were able to demonstrate by polymorphic microsatellite analysis that the defective allele originated from the maternal side. As four brothers and one sister had inherited the same allele, which however was wild type, we were able to show that the mutation must have occurred in the germ cells of the patient's mother and that it may therefore be called de novo. This explains the lack of a high cancer incidence in the family history. All tumours tested showed positive immunohistochemical staining for p53. Loss of heterozygosity was found in five of seven tumours, one showing chromosome 17 monosomy. Nature Publishing Group 1996-07 /pmc/articles/PMC2074589/ /pubmed/8688334 Text en
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Speiser, P. Gharehbaghi-Schnell, E. Eder, S. Haid, A. Kovarík, J. Nenutil, R. Sauter, G. Schneeberger, C. H. Vojtesek, B. Wiltschke, C. H. Zeillinger, R.
spellingShingle	Speiser, P. Gharehbaghi-Schnell, E. Eder, S. Haid, A. Kovarík, J. Nenutil, R. Sauter, G. Schneeberger, C. H. Vojtesek, B. Wiltschke, C. H. Zeillinger, R. A constitutional de novo mutation in exon 8 of the p53 gene in a patient with multiple primary malignancies.
author_facet	Speiser, P. Gharehbaghi-Schnell, E. Eder, S. Haid, A. Kovarík, J. Nenutil, R. Sauter, G. Schneeberger, C. H. Vojtesek, B. Wiltschke, C. H. Zeillinger, R.
author_sort	Speiser, P.
title	A constitutional de novo mutation in exon 8 of the p53 gene in a patient with multiple primary malignancies.
title_short	A constitutional de novo mutation in exon 8 of the p53 gene in a patient with multiple primary malignancies.
title_full	A constitutional de novo mutation in exon 8 of the p53 gene in a patient with multiple primary malignancies.
title_fullStr	A constitutional de novo mutation in exon 8 of the p53 gene in a patient with multiple primary malignancies.
title_full_unstemmed	A constitutional de novo mutation in exon 8 of the p53 gene in a patient with multiple primary malignancies.
title_sort	constitutional de novo mutation in exon 8 of the p53 gene in a patient with multiple primary malignancies.
description	We report a constitutional point mutation of codon 278 in exon 8 of the TP53 gene that has not yet been described as a germ-line mutation. A 52-year-old female developed multiple primary malignancies (liposarcoma, breast cancer, malignant histiocytoma, occult adenocarcinoma). The mutation found in her tumour and peripheral blood lymphocyte DNA is a cytosine to thymine transition at the second position of codon 278 resulting in an amino acid exchange from proline to leucine in the DNA-binding domain. Evaluation of the patient's family revealed that both of her sons were affected by the same mutation. Although the patient's mother had died already, we were able to demonstrate by polymorphic microsatellite analysis that the defective allele originated from the maternal side. As four brothers and one sister had inherited the same allele, which however was wild type, we were able to show that the mutation must have occurred in the germ cells of the patient's mother and that it may therefore be called de novo. This explains the lack of a high cancer incidence in the family history. All tumours tested showed positive immunohistochemical staining for p53. Loss of heterozygosity was found in five of seven tumours, one showing chromosome 17 monosomy.
publisher	Nature Publishing Group
publishDate	1996
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074589/
_version_	1611407790169915392

A constitutional de novo mutation in exon 8 of the p53 gene in a patient with multiple primary malignancies.

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