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Mutations of the p53 tumour suppressor gene in haematologic neoplasms
Author(s) -
Mori Naoki,
Wada Makio,
Yokota Jun,
Terada Masaaki,
Okada Michiko,
Teramura Masanao,
Masuda Michihiko,
Hoshino Shigeru,
Motoji Toshiko,
Oshimi Kazuo,
Mizoguchi Hideaki
Publication year - 1992
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1992.tb08213.x
Subject(s) - missense mutation , carcinogenesis , biology , point mutation , silent mutation , exon , gene , nonsense mutation , genetics , tumor suppressor gene , stop codon , mutation , cancer research , allele
Summary. Mutations of the p53 tumour suppressor gene have frequently been observed in several types of solid tumours and are believed to be implicated in the development of these tumours. To determine the relevance of p53 mutations in haematologic neoplasms, we performed polymerase chain reaction‐single strand conformation polymorphism analysis on the p53 gene in 45 patients with various types of haematologic neoplasms. In exons 5–8 containing highly conserved regions, mobility shifts indicating sequence alterations were detected in four of the 45 patients, and subsequent sequencing was performed. A point mutation resulting in a novel stop codon was detected at codon 213 in one of 23 cases of chronic myelogenous leukaemia (one of five cases of blast crisis). Point mutations causing amino acid substitutions were detected in one of four cases of myelodysplastic syndrome at codon 195, one of three cases of adult T‐cell leukaemia at codon 281, and one of eight cases of acute lymphoblastic leukaemia at codon 281, and these missense mutations were accompanied by loss of the wild type allele. Patients harbouring these nonsense and missense mutations were in advanced disease stages. These findings suggest that mutational inactivation of the p53 gene is infrequent but is involved in the tumorigenesis of several types of haematologic neoplasms at least in some cases.