Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia

C. A. Felix, M. M. Nau, T. Takahashi, T. Mitsudomi, I. Chiba, D. G. Poplack, G. H. Reaman, D. E. Cole, J. J. Letterio, J. Whang-Peng, T. Knutsen, J. D. Minna

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

The p53 gene was examined in primary lymphoblasts of 25 pediatric patients with acute lymphoblastic leukemia by the RNase protection assay and by single strand conformation polymorphism analysis in 23 of 25 cases. p53 mutations were found to occur, but at a low frequency (4 of 25). While all four mutations were identified by single strand conformation polymorphism, the comparative sensitivity of RNase protection was 50% (2 of 4). Heterozygosity was retained at mutated codons in 3 of 4 cases. One pedigree was consistent with the Li-Fraumeni syndrome, and bone marrow from both diagnosis and remission indicated a germline G to T transversion at codon 272 (valine to leucine). Although members of another family were affected with leukemia, a 2-bp deletion in exon 6 was nonhereditary. The other two nonhereditary p53 mutations included a T to G transversion at codon 270 (phenylalanine to cysteine) and a G to C transversion at codon 248 (arginine to proline). These data support the role of both hereditary and acquired p53 mutations in the pathogenesis and/or progression of some cases of childhood acute lymphoblastic leukemia.

Original languageEnglish
Pages (from-to)640-647
Number of pages8
JournalJournal of Clinical Investigation
Volume89
Issue number2
DOIs
Publication statusPublished - Jan 1 1992
Externally publishedYes

Fingerprint

p53 Genes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Codon
Mutation
Ribonucleases
Li-Fraumeni Syndrome
Valine
Pedigree
Phenylalanine
Proline
Leucine
Cysteine
Arginine
Exons
Leukemia
Bone Marrow
Pediatrics

Keywords

  • B-cell precursor
  • Germline
  • Li-Fraumeni syndrome
  • T cell
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Felix, C. A., Nau, M. M., Takahashi, T., Mitsudomi, T., Chiba, I., Poplack, D. G., ... Minna, J. D. (1992). Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia. Journal of Clinical Investigation, 89(2), 640-647. https://doi.org/10.1172/JCI115630

Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia. / Felix, C. A.; Nau, M. M.; Takahashi, T.; Mitsudomi, T.; Chiba, I.; Poplack, D. G.; Reaman, G. H.; Cole, D. E.; Letterio, J. J.; Whang-Peng, J.; Knutsen, T.; Minna, J. D.

In: Journal of Clinical Investigation, Vol. 89, No. 2, 01.01.1992, p. 640-647.

Research output: Contribution to journalArticle

Felix, CA, Nau, MM, Takahashi, T, Mitsudomi, T, Chiba, I, Poplack, DG, Reaman, GH, Cole, DE, Letterio, JJ, Whang-Peng, J, Knutsen, T & Minna, JD 1992, 'Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia', Journal of Clinical Investigation, vol. 89, no. 2, pp. 640-647. https://doi.org/10.1172/JCI115630
Felix CA, Nau MM, Takahashi T, Mitsudomi T, Chiba I, Poplack DG et al. Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia. Journal of Clinical Investigation. 1992 Jan 1;89(2):640-647. https://doi.org/10.1172/JCI115630
Felix, C. A. ; Nau, M. M. ; Takahashi, T. ; Mitsudomi, T. ; Chiba, I. ; Poplack, D. G. ; Reaman, G. H. ; Cole, D. E. ; Letterio, J. J. ; Whang-Peng, J. ; Knutsen, T. ; Minna, J. D. / Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia. In: Journal of Clinical Investigation. 1992 ; Vol. 89, No. 2. pp. 640-647.
@article{cfdaa6b7c2aa4dc998385ff85c594c02,
title = "Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia",
abstract = "The p53 gene was examined in primary lymphoblasts of 25 pediatric patients with acute lymphoblastic leukemia by the RNase protection assay and by single strand conformation polymorphism analysis in 23 of 25 cases. p53 mutations were found to occur, but at a low frequency (4 of 25). While all four mutations were identified by single strand conformation polymorphism, the comparative sensitivity of RNase protection was 50{\%} (2 of 4). Heterozygosity was retained at mutated codons in 3 of 4 cases. One pedigree was consistent with the Li-Fraumeni syndrome, and bone marrow from both diagnosis and remission indicated a germline G to T transversion at codon 272 (valine to leucine). Although members of another family were affected with leukemia, a 2-bp deletion in exon 6 was nonhereditary. The other two nonhereditary p53 mutations included a T to G transversion at codon 270 (phenylalanine to cysteine) and a G to C transversion at codon 248 (arginine to proline). These data support the role of both hereditary and acquired p53 mutations in the pathogenesis and/or progression of some cases of childhood acute lymphoblastic leukemia.",
keywords = "B-cell precursor, Germline, Li-Fraumeni syndrome, T cell, Tumor suppressor gene",
author = "Felix, {C. A.} and Nau, {M. M.} and T. Takahashi and T. Mitsudomi and I. Chiba and Poplack, {D. G.} and Reaman, {G. H.} and Cole, {D. E.} and Letterio, {J. J.} and J. Whang-Peng and T. Knutsen and Minna, {J. D.}",
year = "1992",
month = "1",
day = "1",
doi = "10.1172/JCI115630",
language = "English",
volume = "89",
pages = "640--647",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "2",

}

TY - JOUR

T1 - Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia

AU - Felix, C. A.

AU - Nau, M. M.

AU - Takahashi, T.

AU - Mitsudomi, T.

AU - Chiba, I.

AU - Poplack, D. G.

AU - Reaman, G. H.

AU - Cole, D. E.

AU - Letterio, J. J.

AU - Whang-Peng, J.

AU - Knutsen, T.

AU - Minna, J. D.

PY - 1992/1/1

Y1 - 1992/1/1

N2 - The p53 gene was examined in primary lymphoblasts of 25 pediatric patients with acute lymphoblastic leukemia by the RNase protection assay and by single strand conformation polymorphism analysis in 23 of 25 cases. p53 mutations were found to occur, but at a low frequency (4 of 25). While all four mutations were identified by single strand conformation polymorphism, the comparative sensitivity of RNase protection was 50% (2 of 4). Heterozygosity was retained at mutated codons in 3 of 4 cases. One pedigree was consistent with the Li-Fraumeni syndrome, and bone marrow from both diagnosis and remission indicated a germline G to T transversion at codon 272 (valine to leucine). Although members of another family were affected with leukemia, a 2-bp deletion in exon 6 was nonhereditary. The other two nonhereditary p53 mutations included a T to G transversion at codon 270 (phenylalanine to cysteine) and a G to C transversion at codon 248 (arginine to proline). These data support the role of both hereditary and acquired p53 mutations in the pathogenesis and/or progression of some cases of childhood acute lymphoblastic leukemia.

AB - The p53 gene was examined in primary lymphoblasts of 25 pediatric patients with acute lymphoblastic leukemia by the RNase protection assay and by single strand conformation polymorphism analysis in 23 of 25 cases. p53 mutations were found to occur, but at a low frequency (4 of 25). While all four mutations were identified by single strand conformation polymorphism, the comparative sensitivity of RNase protection was 50% (2 of 4). Heterozygosity was retained at mutated codons in 3 of 4 cases. One pedigree was consistent with the Li-Fraumeni syndrome, and bone marrow from both diagnosis and remission indicated a germline G to T transversion at codon 272 (valine to leucine). Although members of another family were affected with leukemia, a 2-bp deletion in exon 6 was nonhereditary. The other two nonhereditary p53 mutations included a T to G transversion at codon 270 (phenylalanine to cysteine) and a G to C transversion at codon 248 (arginine to proline). These data support the role of both hereditary and acquired p53 mutations in the pathogenesis and/or progression of some cases of childhood acute lymphoblastic leukemia.

KW - B-cell precursor

KW - Germline

KW - Li-Fraumeni syndrome

KW - T cell

KW - Tumor suppressor gene

UR - http://www.scopus.com/inward/record.url?scp=0026577713&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026577713&partnerID=8YFLogxK

U2 - 10.1172/JCI115630

DO - 10.1172/JCI115630

M3 - Article

C2 - 1737852

AN - SCOPUS:0026577713

VL - 89

SP - 640

EP - 647

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 2

ER -