Journal Article

Centromere fission, not telomere erosion, triggers chromosomal instability in human carcinomas

Carlos Martínez-A and Karel H.M. van Wely

in Carcinogenesis

Volume 32, issue 6, pages 796-803
Published in print June 2011 | ISSN: 0143-3334
Published online April 2011 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgr069

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

The majority of sporadic carcinomas suffer from a kind of genetic instability in which chromosome number changes occur together with segmental defects. This means that changes involving intact chromosomes accompany breakage-induced alterations. Whereas the causes of aneuploidy are described in detail, the origins of chromosome breakage in sporadic carcinomas remain disputed. The three main pathways of chromosomal instability (CIN) proposed until now (random breakage, telomere fusion and centromere fission) are largely based on animal models and in vitro experiments, and recent studies revealed several discrepancies between animal models and human cancer. Here, we discuss how the experimental systems translate to human carcinomas and compare the theoretical breakage products to data from patient material and cancer cell lines. The majority of chromosomal defects in human carcinomas comprises pericentromeric breaks that are captured by healthy telomeres, and only a minor proportion of chromosome fusions can be attributed to telomere erosion or random breakage. Centromere fission, not telomere erosion, is therefore the most probably trigger of CIN and early carcinogenesis. Similar centromere–telomere fusions might drive a subset of congenital defects and evolutionary chromosome changes.

Journal Article.  6795 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.