© 2006 European Society for Medical Oncology
symposium article |
Patterns of genomic instability in gastric cancer: clinical implications and perspectives
1 Department of Experimental Medicine and Pathology, University ‘La Sapienza’, Rome; 2 Department of Oncology and Neurosciences, University ‘G. D'Annunzio’, Chieti; 3 Section of Medical Oncology, Department of Surgical and Oncology, Università di Palermo; 4 Division of Medical Oncology, National Institute of Oncology, Bari, Italy
* Correspondence to: Prof. L. Ottini, Department of Experimental Medicine and Pathology, University ‘La Sapienza’, Viale Regina Elena 324, 00161 Rome, Italy. Tel: +39-0649973009; Fax: +39-064454820; E-mail: laura.ottini{at}uniroma1.it
In gastric cancer (GC) the loss of genomic stability represents a key molecular step that occurs early in the carcinogenesis process and creates a permissive environment for the accumulation of genetic and epigenetic alterations in tumor suppressor genes and oncogenes. It is widely accepted that GC can follow at least two major genomic instability pathways, microsatellite instability (MSI) and chromosome instability (CIN). MSI is responsible for a well-defined subset of GCs. CIN represents a more common pathway comprising heterogeneous subsets of GC. In addition to MSI and CIN, the CpG islands methylator phenotype (CIMP) plays an important role in gastric carcinogenesis. CIMP may lead to the transcriptional silencing of various genes in gastric carcinogenesis. Intriguingly, more recently in addition to CpG island hypermethylation, a global DNA demethylation, that precedes genomic damage, has been observed in GC. Thus, epigenetic alterations may play a relevant role in gastric carcinogenesis as alternative mechanisms. Evidence suggests that although MSI, CIN and CIMP phenotypes can be distinguished from one another, there might be some degree of overlap. This review describes our current knowledge of the instability pathways in gastric carcinogenesis and the potential clinical applications for different forms of genomic instability in GC.
Key words: gastric cancer, genomic instability, microsatellite instability (MSI), chromosomal instability (CIN), CpG island methylator phenotype (CIMP), clinical implications
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