PMID- 10616528
OWN - NLM
STAT- MEDLINE
DCOM- 20000113
LR  - 20190816
IS  - 0165-4608 (Print)
IS  - 0165-4608 (Linking)
VI  - 116
IP  - 1
DP  - 2000 Jan 1
TI  - Complete loss of wild-type TP53 in a nontransformed human epithelial cell line is 
      preceded by a phase during which a heterozygous TP53 mutant effectively outgrows 
      the homozygous wild-type cells.
PG  - 28-34
AB  - HMT-3522 is a spontaneously immortalized cell line derived from a fibrocystic 
      breast lesion. After continuous accumulation of genetic changes, the cell line 
      was transformed from a nontumorigenic to a malignant phenotype. One of the 
      earliest genetic aberrations is a missense mutation of codon 179 (His179Asn) in 
      the tumor suppressor gene TP53 leading to outgrowth of a cell type expressing 
      only the mutant form of TP53. In this report, we extend earlier investigations to 
      reveal the genetic background for the evolution from homozygous wild type to 
      hemizygous mutated cells. The status of the TP53 alleles was followed at 
      different stages by fluorescence in situ hybridization (FISH) and allele-specific 
      PCR (ASPCR) on total DNA, as well as flow-sorted chromosomes--taking advantage of 
      a size difference between the two homologues of chromosome 17 that harbor TP53 on 
      17p. This further allowed us to determine on which of the two chromosomes the 
      mutated allele was located. The results presented here show that the cells have 
      undergone an evolution from homozygous wild type for TP53 to heterozygous 
      (His179Asn mutation in one allele), and finally to a hemizygous mutated state 
      (deletion of the remaining wild-type allele). The finding of a transient period 
      in which heterozygous cells dominate the population before the eventual outgrowth 
      of hemizygous cells strongly indicates that the His179Asn mutation results in a 
      tp53 protein with a dominant negative effect that does not totally abrogate the 
      function of wild type TP53 in vitro.
FAU - Villadsen, R
AU  - Villadsen R
AD  - Department of Tumor Endocrinology, Danish Cancer Society, Copenhagen, Denmark.
FAU - Nielsen, K V
AU  - Nielsen KV
FAU - Bolund, L
AU  - Bolund L
FAU - Briand, P
AU  - Briand P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Genet Cytogenet
JT  - Cancer genetics and cytogenetics
JID - 7909240
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Alleles
MH  - Breast/chemistry/*cytology
MH  - Cell Division
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - Chromosomes, Human, Pair 17
MH  - DNA/analysis
MH  - Epithelial Cells
MH  - Female
MH  - Fibrocystic Breast Disease/genetics
MH  - Flow Cytometry
MH  - *Genes, p53
MH  - Genotype
MH  - Heterozygote
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Mutation, Missense
MH  - Polymerase Chain Reaction
MH  - Tumor Suppressor Protein p53/physiology
EDAT- 2000/01/05 00:00
MHDA- 2000/01/05 00:01
CRDT- 2000/01/05 00:00
PHST- 2000/01/05 00:00 [pubmed]
PHST- 2000/01/05 00:01 [medline]
PHST- 2000/01/05 00:00 [entrez]
AID - S0165-4608(99)00112-0 [pii]
AID - 10.1016/s0165-4608(99)00112-0 [doi]
PST - ppublish
SO  - Cancer Genet Cytogenet. 2000 Jan 1;116(1):28-34. doi: 
      10.1016/s0165-4608(99)00112-0.