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Nat Rev Cancer. 2001 Dec;1(3):214-21. doi: 10.1038/35106058.

FRA3B and other common fragile sites: the weakest links.

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Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.


In 1979, the first chromosome alteration associated with familial cancer was reported. Five years later, a fragile site was observed in the same chromosome region. The product of the fragile histidine triad (FHIT) gene, which encompasses this fragile site, is partially or entirely lost in most human cancers, indicating that it has a tumour-suppressor function. Inactivation of only one FHIT allele compromises this suppressor function, indicating that a 'one-hit' mechanism of tumorigenesis is operative. Are genes disrupted at other fragile sites? And, are these genes also tumour suppressors?

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