Genomic instability — an evolving hallmark of cancer

Genomic instability as a hallmark of cancer. a) A proposed revision of the hallmarks of cancer to include genomic instability, and to consolidate the self-sufficiency in growth signals and insensitivity to anti-growth signals into the single hallmark of activated growth signalling. The secondary hallmarks (oxidative stress and proteotoxic stress) are shown separately. b) The temporal order by which the hallmarks are acquired in hereditary cancers. The establishment of genomic instability is probably the initiating event, which then facilitates the establishment of all the other hallmarks. c) The temporal order by which the hallmarks are acquired in sporadic (non-hereditary) cancers. Deregulation of growth-regulating genes can be the initiating event. This leads to DNA damage and DNA replication stress, which, in turn, lead to genomic instability and selective pressure for tumour suppressor p53 (TP53) inactivation. Loss of p53 function allows evasion from cell death, whereas the genomic instability provides a fertile ground for additional mutations that lead to the establishment of the remaining hallmarks, as in hereditary cancers (1). [Figure in part a) is modified, with permission, from REF 59 © (2009) Elsevier of (1)]

1) Negrini et al. Genomic instability--an evolving hallmark of cancer. Nat Rev Mol Cell Biol. 2010, 11(3): 220-8.

VG New

Prof. Vassilis G. Gorgoulis

Laboratory of Histology-Embryology
Molecular Carcinogenesis Group
Medical School
National and Kapodistrian University of Athens



Chair of Clinical Molecular Pathology,

Ninewells Hospital and School of Medicine


University of Dundee, Dundee, UK


Biomedical Research Foundation of the Academy of Athens


Faculty Institute for Cancer Sciences, University of Manchester,
Manchester Academic Health Science Centre, Manchester, UK

Manchester Centre for Cellular Metabolism,
University of Manchester, Manchester Academic Health Science Centre, Manchester


EMBO member


European Academy
of Cancer Sciences member


Academia Europaea member, 180 Varick Street, 6th Floor, New York, NY 10014, USA 






Office Tel: 0030 210-7462352
Fax: 0030 210-7462340


Error: No articles to display

Also see...


Copyright ©2011-2015, Prof. Gorgoulis Powered by AVMap