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Review
. 2014 Dec;71(23):4601-15.
doi: 10.1007/s00018-014-1753-6. Epub 2014 Oct 10.

Very large common fragile site genes and their potential role in cancer development

Ge Gao  1 , David I Smith
Affiliations
Review

Very large common fragile site genes and their potential role in cancer development

Ge Gao et al. Cell Mol Life Sci. 2014 Dec.

Abstract

Common fragile sites (CFSs) are large chromosomal regions that are hot-spots for alterations especially within cancer cells. The three most frequently expressed CFS regions (FRA3B, FRA16D and FRA6E) contain genes that span extremely large genomic regions (FHIT, WWOX and PARK2, respectively), and these genes were found to function as important tumor suppressors. Many other CFS regions contain extremely large genes that are also targets of alterations in multiple cancers, but none have yet been demonstrated to function as tumor suppressors. The loss of expression of just FHIT or WWOX has been found to be associated with a worse overall clinical outcome. Studies in different cancers have revealed that some cancers have decreased expression of multiple large CFS genes. This loss of expression could have a profound phenotypic effect on these cells. In this review, we will summarize the known large common fragile site genes and discuss their potential relationship to cancer development.

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Figures

Fig. 1
Fig. 1
Comparison ideograms and diagrams of common fragile sites FRA16D and FRA8E from human and mouse. Top the relative chromosome location of human common fragile site FRA16D and its associated gene WWOX. Bottom the relative chromosome location of mouse common fragile site FRA8E and its associated gene Wwox (the ideograms of human chromosome 16 and mouse chromosome 8 are retrieved from NCBI website. The diagrams of the human common fragile sites FRA16D and mouse FRA8E are taken from Krummel et al. [49]). Also included on this figure are the BAC clones utilized to characterize each CFS region and the number of times that that BAC clone was found to hybridize proximal, crossing or distal to the region of decondensation/breakage in specific metaphases
Fig. 2
Fig. 2
RNA sequencing revealed that different common fragile sites genes showed different expression pattern in examined oropharyngeal squamous cancer samples. The RNA sequencing data were analyzed using Geospiza Genesifter analysis pipeline. The pipeline generated each gene’s average expression in tumor group and normal group. The figure is represented in log2 format
See this image and copyright information in PMC

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