The TP53 Codon 72 Polymorphism May Affect the Function of TP53 Mutations in Breast Carcinomas but not in Colorectal Carcinomas

The TP53 Codon 72 Polymorphism May Affect the Function of TP53 Mutations in Breast Carcinomas but not in Colorectal Carcinomas1

Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, 0310 Oslo, Norway [A. L., I. R. K. B., A. B., T. I. A., R. A. L., A-L. B. D.]; Department of Oncology, Haukeland University Hospital, Bergen, Norway [P. E. L.]; and Institute for Forensic Medicine, The National Hospital, Oslo, Norway [T. O. R., G. I. M.]

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.

Footnotes

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↵1 This study was supported by grants from the Norwegian Cancer Society, The Research Council of Norway, and the Norwegian Women’s Public Health Organization. A. L. is a research fellow of the Norwegian Cancer Society.
↵2 Present address: Department of Surgery, Akershus University Hospital, 1474 Nordbyhagen, Norway.
↵3 Present address: Department of Oncology, Ullevål University Hospital, 0407 Oslo, Norway.
↵4 To whom requests for reprints should be addressed, at Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway. Phone: 47-22-93-44-19; Fax: 47-22-93-44-40; E-mail: a.l.b.dale{at}labmed.uio.no
↵5 Internet address: www.iarc.fr/P53/index.html.
↵6 Internet address: www.iarc.fr/P53/index.html.
- Accepted September 16, 1902.
- Received November 30, 1901.
- Revision received July 26, 1902.