Absence of hereditary p53 mutations in 10 familial leukemia pedigrees

Carolyn A. Felix, Domenico D'Amico, Tetsuya Mitsudomi, Marion M. Nau, Frederick P. Li, Joseph F. Fraumeni, Díane E. Cole, June McCalla, Gregory H. Reaman, Jacqueline Whang-Peng, Turid Knutsen, John D. Minna, David G. Poplack

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Germline p53 mutations have been identified in the Li-Fraumeni syndrome but the role of such mutations in familial leukemia is not established. The p53 gene was examined by single-strand conformation polymorphism analysis of exons 4-8 in 10 families with multiple members affected with leukemia. The diagnoses included acute and chronic leukemias and Hodgkin's disease. Identified in two families were p53 mutations that were nonnhereditary. These included a 2-bp deletion in exon 6 found in the lymphoblast DNA of one child whose sibling, cousin, and several adult relatives had acute leukemia. The other nonhereditary p53 mutation was a transition at codon 248 (CGG to CAG, arginine to glutamine) found in the lymphoblasts of a patient with a preleukemic syndrome and acute lymphoblastic leukemia (ALL) whose brother is a long-term survivor of ALL. Thus, p53 mutations were found to occur in two families but both were nonhereditary. Moreover, in the remaining eight famlies no p53 mutation was identified in the regions of p53 where most mutations have been found in other cancers. Although p53 mutations sometimes may be present, they do not appear to be a primary event responsible for hereditary susceptibility to familial leukemia. This study suggests involvement of other genes or Mechanisms.

Original languageEnglish (US)
Pages (from-to)653-658
Number of pages6
JournalJournal of Clinical Investigation
Volume90
Issue number2
StatePublished - 1992

Fingerprint

Pedigree
Leukemia
Mutation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Siblings
Exons
Li-Fraumeni Syndrome
Germ-Line Mutation
p53 Genes
Glutamine
Hodgkin Disease
Codon
Survivors
Arginine
Chronic Disease
DNA
Genes
Neoplasms

Keywords

  • Acute lymphoblastic leukemia
  • Germline mutation
  • Somatic mutation
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Felix, C. A., D'Amico, D., Mitsudomi, T., Nau, M. M., Li, F. P., Fraumeni, J. F., ... Poplack, D. G. (1992). Absence of hereditary p53 mutations in 10 familial leukemia pedigrees. Journal of Clinical Investigation, 90(2), 653-658.

Absence of hereditary p53 mutations in 10 familial leukemia pedigrees. / Felix, Carolyn A.; D'Amico, Domenico; Mitsudomi, Tetsuya; Nau, Marion M.; Li, Frederick P.; Fraumeni, Joseph F.; Cole, Díane E.; McCalla, June; Reaman, Gregory H.; Whang-Peng, Jacqueline; Knutsen, Turid; Minna, John D.; Poplack, David G.

In: Journal of Clinical Investigation, Vol. 90, No. 2, 1992, p. 653-658.

Research output: Contribution to journalArticle

Felix, CA, D'Amico, D, Mitsudomi, T, Nau, MM, Li, FP, Fraumeni, JF, Cole, DE, McCalla, J, Reaman, GH, Whang-Peng, J, Knutsen, T, Minna, JD & Poplack, DG 1992, 'Absence of hereditary p53 mutations in 10 familial leukemia pedigrees', Journal of Clinical Investigation, vol. 90, no. 2, pp. 653-658.
Felix CA, D'Amico D, Mitsudomi T, Nau MM, Li FP, Fraumeni JF et al. Absence of hereditary p53 mutations in 10 familial leukemia pedigrees. Journal of Clinical Investigation. 1992;90(2):653-658.
Felix, Carolyn A. ; D'Amico, Domenico ; Mitsudomi, Tetsuya ; Nau, Marion M. ; Li, Frederick P. ; Fraumeni, Joseph F. ; Cole, Díane E. ; McCalla, June ; Reaman, Gregory H. ; Whang-Peng, Jacqueline ; Knutsen, Turid ; Minna, John D. ; Poplack, David G. / Absence of hereditary p53 mutations in 10 familial leukemia pedigrees. In: Journal of Clinical Investigation. 1992 ; Vol. 90, No. 2. pp. 653-658.
@article{a6b506cb69a741c2b5eecc9d08e3d0b5,
title = "Absence of hereditary p53 mutations in 10 familial leukemia pedigrees",
abstract = "Germline p53 mutations have been identified in the Li-Fraumeni syndrome but the role of such mutations in familial leukemia is not established. The p53 gene was examined by single-strand conformation polymorphism analysis of exons 4-8 in 10 families with multiple members affected with leukemia. The diagnoses included acute and chronic leukemias and Hodgkin's disease. Identified in two families were p53 mutations that were nonnhereditary. These included a 2-bp deletion in exon 6 found in the lymphoblast DNA of one child whose sibling, cousin, and several adult relatives had acute leukemia. The other nonhereditary p53 mutation was a transition at codon 248 (CGG to CAG, arginine to glutamine) found in the lymphoblasts of a patient with a preleukemic syndrome and acute lymphoblastic leukemia (ALL) whose brother is a long-term survivor of ALL. Thus, p53 mutations were found to occur in two families but both were nonhereditary. Moreover, in the remaining eight famlies no p53 mutation was identified in the regions of p53 where most mutations have been found in other cancers. Although p53 mutations sometimes may be present, they do not appear to be a primary event responsible for hereditary susceptibility to familial leukemia. This study suggests involvement of other genes or Mechanisms.",
keywords = "Acute lymphoblastic leukemia, Germline mutation, Somatic mutation, Tumor suppressor gene",
author = "Felix, {Carolyn A.} and Domenico D'Amico and Tetsuya Mitsudomi and Nau, {Marion M.} and Li, {Frederick P.} and Fraumeni, {Joseph F.} and Cole, {D{\'i}ane E.} and June McCalla and Reaman, {Gregory H.} and Jacqueline Whang-Peng and Turid Knutsen and Minna, {John D.} and Poplack, {David G.}",
year = "1992",
language = "English (US)",
volume = "90",
pages = "653--658",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "2",

}

TY - JOUR

T1 - Absence of hereditary p53 mutations in 10 familial leukemia pedigrees

AU - Felix, Carolyn A.

AU - D'Amico, Domenico

AU - Mitsudomi, Tetsuya

AU - Nau, Marion M.

AU - Li, Frederick P.

AU - Fraumeni, Joseph F.

AU - Cole, Díane E.

AU - McCalla, June

AU - Reaman, Gregory H.

AU - Whang-Peng, Jacqueline

AU - Knutsen, Turid

AU - Minna, John D.

AU - Poplack, David G.

PY - 1992

Y1 - 1992

N2 - Germline p53 mutations have been identified in the Li-Fraumeni syndrome but the role of such mutations in familial leukemia is not established. The p53 gene was examined by single-strand conformation polymorphism analysis of exons 4-8 in 10 families with multiple members affected with leukemia. The diagnoses included acute and chronic leukemias and Hodgkin's disease. Identified in two families were p53 mutations that were nonnhereditary. These included a 2-bp deletion in exon 6 found in the lymphoblast DNA of one child whose sibling, cousin, and several adult relatives had acute leukemia. The other nonhereditary p53 mutation was a transition at codon 248 (CGG to CAG, arginine to glutamine) found in the lymphoblasts of a patient with a preleukemic syndrome and acute lymphoblastic leukemia (ALL) whose brother is a long-term survivor of ALL. Thus, p53 mutations were found to occur in two families but both were nonhereditary. Moreover, in the remaining eight famlies no p53 mutation was identified in the regions of p53 where most mutations have been found in other cancers. Although p53 mutations sometimes may be present, they do not appear to be a primary event responsible for hereditary susceptibility to familial leukemia. This study suggests involvement of other genes or Mechanisms.

AB - Germline p53 mutations have been identified in the Li-Fraumeni syndrome but the role of such mutations in familial leukemia is not established. The p53 gene was examined by single-strand conformation polymorphism analysis of exons 4-8 in 10 families with multiple members affected with leukemia. The diagnoses included acute and chronic leukemias and Hodgkin's disease. Identified in two families were p53 mutations that were nonnhereditary. These included a 2-bp deletion in exon 6 found in the lymphoblast DNA of one child whose sibling, cousin, and several adult relatives had acute leukemia. The other nonhereditary p53 mutation was a transition at codon 248 (CGG to CAG, arginine to glutamine) found in the lymphoblasts of a patient with a preleukemic syndrome and acute lymphoblastic leukemia (ALL) whose brother is a long-term survivor of ALL. Thus, p53 mutations were found to occur in two families but both were nonhereditary. Moreover, in the remaining eight famlies no p53 mutation was identified in the regions of p53 where most mutations have been found in other cancers. Although p53 mutations sometimes may be present, they do not appear to be a primary event responsible for hereditary susceptibility to familial leukemia. This study suggests involvement of other genes or Mechanisms.

KW - Acute lymphoblastic leukemia

KW - Germline mutation

KW - Somatic mutation

KW - Tumor suppressor gene

UR - http://www.scopus.com/inward/record.url?scp=0026658152&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026658152&partnerID=8YFLogxK

M3 - Article

C2 - 1644930

AN - SCOPUS:0026658152

VL - 90

SP - 653

EP - 658

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 2

ER -