1. ¹Unité d'Oncologie Moléculaire, INSERM U590, Centre Léon Bérard, 28 rue Laënnec, 69373 Lyon Cedex 08, France
2. ²Faculté de Pharmacie, 8 avenue Rockefeller, 69373 Lyon Cedex 08, France
3. ³Fédération de Spécialités Digestives, Hôpital Edouard Herriot, Place d'Arsonval, 69437 Lyon Cedex 03, France

Correspondence: A Puisieux, E-mail: puisieux@lyon.fnclcc.fr

Received 20 May 2003; Revised 4 August 2003; Accepted 5 August 2003.

Abstract

Numerous observations suggest that chromosome instability is caused by mitotic abnormalities such as errors in the partitioning of chromosomes. Chfr was recently defined as a central component of a new mitotic checkpoint that delays chromosome condensation in response to mitotic stress. Chfr was shown to be frequently inactivated in several human neoplasms, including colon, lung and esophageal cancers. To test whether Chfr inactivation may lead or participate to chromosomal instability (CIN), we analysed the genetic and epigenetic status of the gene in a large panel of primary colon and breast cancers, as well as in colon and breast cancer cell lines displaying either a microsatellite instability or a CIN. Our results confirm that Chfr is frequently inactivated in colon cancers, through a mechanism of hypermethylation of the promoter sequences. In contrast, the loss of Chfr expression appears to be a rare event in breast cancers. Furthermore, our data demonstrate that Chfr inactivation is not associated with CIN in these frequent types of human cancers.