p53 mutations occur in aggressive breast cancer.
Using a polymerase chain reaction-single strand conformation polymorphism approach we analyzed 96 human primary breast tumors for the presence of mutations in exons 2, 5, 6, 7, 8, and 9 of the p53 gene. These exons have been shown to comprise highly conserved sequences and the portion including exons 5 through 9 is believed to be the target for over 90% of the acquired mutations in human cancer. Eighteen tumors of the 96 (18.7%) tested showed reproducibly a variant band indicative of a mutation. Most (15 tumors) of the mutations were single nucleotide substitutions and G:C to A:T transitions were prevalent (6 tumors), G:C to T:A transversions came next (4 tumors), and guanines were always on the nontranscribed strand. Concomitant loss of the wild type allele and mutation of the other copy was observed in only 3 of 18 mutated cases; this is consistent with the heterogeneous cellular composition of breast tumors. Furthermore p53 mutations were correlated to estrogen and/or progesterone receptor negative tumors, thus indicating their relationships to aggressive breast cancer. No association could be observed with DNA amplification events in these tumors.
Mazars
R
R
CNRS URA 1191, Université Montpellier II, France.
Spinardi
L
L
BenCheikh
M
M
Simony-Lafontaine
J
J
Jeanteur
P
P
Theillet
C
C
D001943:Breast Neoplasms / Q000235:genetics*; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction