title: The TP53 codon 72 polymorphism may affect the function of TP53 mutations in breast carcinomas but not in colorectal carcinomas.
abstract: An Arg/Pro polymorphism in codon 72 of the TP53 gene was analyzed in blood samples from 390 breast and 162 colorectal cancer patients previously investigated for TP53 mutations in their tumors. Among the breast cancer cases, 228 were homozygous for the Arg72 allele, of which, 65 (28.5%) also had a TP53 mutation in their tumors. In contrast, of 26 cases that were homozygous for the Pro72 allele, only 1 case (3.8%) had a TP53 mutation in the tumor (P = 0.004). Cloning the TP53 gene from tumor DNA followed by sequencing was performed in 14 heterozygotes with tumor mutation, and 9 of the mutations resided on the Arg72 allele. Among the colorectal cancer cases, no difference in mutation frequency was seen between the two different homozygotes, 40 TP53 mutations in 97 Arg72 homozygous cases (41.2%) versus 7 in 16 Pro72 homozygous cases (43.8%). These results suggest a selective growth advantage for cells carrying a type of TP53 mutation seen in breast carcinomas when the mutation resides on an Arg72 allele.
authors.affiliation: Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, 0310 Oslo, Norway.
authors.forename: Anita
authors.initials: A
authors.lastname: Langerød
authors.forename: Ida R K
authors.initials: IR
authors.lastname: Bukholm
authors.forename: André
authors.initials: A
authors.lastname: Bregård
authors.forename: Per Eystein
authors.initials: PE
authors.lastname: Lønning
authors.forename: Tone Ikdal
authors.initials: TI
authors.lastname: Andersen
authors.forename: Torleiv O
authors.initials: TO
authors.lastname: Rognum
authors.forename: Gunn Iren
authors.initials: GI
authors.lastname: Meling
authors.forename: Ragnhild A
authors.initials: RA
authors.lastname: Lothe
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
mesh_terms: D000483:Alleles; D001120:Arginine / Q000235:genetics*; D001483:Base Sequence; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D003062:Codon; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D015994:Incidence; D019656:Loss of Heterozygosity; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D011446:Prospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D003062:Codon; D001120:Arginine