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A novel p53 germline alteration identified in a late onset breast cancer kindred

Sun, X F; Johannsson, O LU ; Håkansson, S LU ; Sellberg, G LU ; Nordenskjöld, B; Olsson, H LU and Borg, A LU (1996) In Oncogene 13(2). p.11-407
Abstract

Germline mutations in the p53 tumor suppressor gene are associated with the Li-Fraumeni syndrome, characterized by childhood sarcoma, leukemia and early onset breast cancer and has occasionally been found also in familial breast-ovarian cancer. Most mutations found are of missense type and located in the central region of the gene (exons 5 to 8). In the present study, a germline p53 alteration was identified in a late onset breast cancer family (kindred Lund 5; mean age 58 years) using single stranded conformation polymorphism and sequence analysis. The mutation (a CCG to CTG transition) at codon 82 in exon 4, resulting in a proline to leucine substitution, has not previously been reported and was not present in a control set of 60... (More)

Germline mutations in the p53 tumor suppressor gene are associated with the Li-Fraumeni syndrome, characterized by childhood sarcoma, leukemia and early onset breast cancer and has occasionally been found also in familial breast-ovarian cancer. Most mutations found are of missense type and located in the central region of the gene (exons 5 to 8). In the present study, a germline p53 alteration was identified in a late onset breast cancer family (kindred Lund 5; mean age 58 years) using single stranded conformation polymorphism and sequence analysis. The mutation (a CCG to CTG transition) at codon 82 in exon 4, resulting in a proline to leucine substitution, has not previously been reported and was not present in a control set of 60 healthy individuals. Three of five woman with breast cancer (45, 57 and 65 years) were carriers of the alteration. Loss of heterozygosity at the p53 locus was not seen in the primary tumors of these women, but appeared as a partial loss of the wildtype allele in subsequent recurrent lesions of two gene carriers. The family manifested no linkage to the p53 gene (a two-point LOD-score of -0.41), and has previously also been excluded for linkage to the BRCA1 and BRCA2 loci, as well as being carrier of a BRCA1 germline mutation. Although it seems unlikely that the p53 germline mutation is the major cause of disease predisposition in Lund 5, the data suggest that some p53 alteration may confer a subtle influence on breast cancer development and progression.

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published
subject
keywords
Aged, Base Sequence, Breast Neoplasms, DNA, Neoplasm, DNA, Satellite, Female, Genes, p53, Genetic Linkage, Germ-Line Mutation, Humans, Male, Middle Aged, Molecular Sequence Data, Pedigree
in
Oncogene
volume
13
issue
2
pages
5 pages
publisher
Nature Publishing Group
external identifiers
  • Scopus:0029787301
ISSN
0950-9232
language
English
LU publication?
yes
id
0340f2bb-0510-48c3-bdd5-3ee3f6e5601c
date added to LUP
2016-09-18 12:51:20
date last changed
2016-10-30 04:49:53
@misc{0340f2bb-0510-48c3-bdd5-3ee3f6e5601c,
  abstract     = {<p>Germline mutations in the p53 tumor suppressor gene are associated with the Li-Fraumeni syndrome, characterized by childhood sarcoma, leukemia and early onset breast cancer and has occasionally been found also in familial breast-ovarian cancer. Most mutations found are of missense type and located in the central region of the gene (exons 5 to 8). In the present study, a germline p53 alteration was identified in a late onset breast cancer family (kindred Lund 5; mean age 58 years) using single stranded conformation polymorphism and sequence analysis. The mutation (a CCG to CTG transition) at codon 82 in exon 4, resulting in a proline to leucine substitution, has not previously been reported and was not present in a control set of 60 healthy individuals. Three of five woman with breast cancer (45, 57 and 65 years) were carriers of the alteration. Loss of heterozygosity at the p53 locus was not seen in the primary tumors of these women, but appeared as a partial loss of the wildtype allele in subsequent recurrent lesions of two gene carriers. The family manifested no linkage to the p53 gene (a two-point LOD-score of -0.41), and has previously also been excluded for linkage to the BRCA1 and BRCA2 loci, as well as being carrier of a BRCA1 germline mutation. Although it seems unlikely that the p53 germline mutation is the major cause of disease predisposition in Lund 5, the data suggest that some p53 alteration may confer a subtle influence on breast cancer development and progression.</p>},
  author       = {Sun, X F and Johannsson, O and Håkansson, S and Sellberg, G and Nordenskjöld, B and Olsson, H and Borg, A},
  issn         = {0950-9232},
  keyword      = {Aged,Base Sequence,Breast Neoplasms,DNA, Neoplasm,DNA, Satellite,Female,Genes, p53,Genetic Linkage,Germ-Line Mutation,Humans,Male,Middle Aged,Molecular Sequence Data,Pedigree},
  language     = {eng},
  month        = {07},
  number       = {2},
  pages        = {11--407},
  publisher    = {ARRAY(0x9654718)},
  series       = {Oncogene},
  title        = {A novel p53 germline alteration identified in a late onset breast cancer kindred},
  volume       = {13},
  year         = {1996},
}