Molecular cytogenetic characterization of a translocation t(13;22)(q22.3;q11.23) in a patient with idiopathic partial epilepsy.

PURPOSE: We report on a balanced de novo translocation t(13;22)(q22.3;q11.23) in a patient with a form of focal idiopathic epilepsy. Since candidate genes for FPEVF (familial partial epilepsy with variable foci) have been mapped by linkage studies in the same cytogenetic band of chromosome 22 involved in the translocation, this case can be helpful to identify genes involved in this form of epilepsy. METHODS: Molecular cytogenetics analyses (FISH and array-CGH) were performed. RESULTS AND CONCLUSIONS: Neither DNA duplications nor deletions were detected by array-CGH, thus it can be inferred that the translocation is balanced. The breakpoint on chromosome 22 was precisely mapped by FISH on the RP11-432I9 clone, which is located in the interval defined by the linkage studies for FPEVF. The role of the known or hypothetical genes next to the 22q breakpoint is discussed.

Chromosomal fragile sites FRA3B and FRA16D show correlated expression and association with failure of apoptosis in lymphocytes from patients with thyroid cancer.

It has been suggested that common fragile sites (cFSs) are related to cancer development. This appears to be the case for FRA3B and FRA16D, localized in two tumor-suppressor genes (FHIT and WWOX, respectively) that are altered by deletions or loss of heterozygosity (LOH) in many cancers. The features responsible for fragility have not yet been identified. Furthermore, it is still unclear whether instability at these regions causes chance deletions and loss of function of the associated genes, or whether the gene function itself is related to the appearance of fragility. In this study, we analyzed cFS expression in lymphocytes from 20 healthy or thyroid cancer-affected subjects exposed to radiation after the Chernobyl accident. The same cells were examined for apoptosis, a principal function of both the FHIT and WWOX genes. Exceptionally elevated chromosome fragility was observed, particularly in cancer patients, affecting FRA3B, FRA16D, and a cluster of less highly expressed cFSs; levels of chromosome fragility were found to be correlated among these cFSs. Interestingly, most expressed cFSs were sites of LOH reported for thyroid tumors; moreover, cells with the highest fragility also had a reduced ability to undergo apoptosis. These findings reveal previously unknown genetic interactions affecting fragile loci, suggestive of a shared function inside mitotic cells. Attenuation of checkpoint control and apoptosis resistance seem to be the cell phenotypes associated with unusual chromosome fragility. We propose that breakage at specific cFS could derive from early epigenetic events at loci involved in radiation carcinogenesis. This article contains supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.