Common fragile sites associated with the breakpoints of chromosomal aberrations in hematologic neoplasms

Fragile sites are specific regions of chromosomes prone to breakage when cells are cultured under specific conditions. These sites are divided into two classes: common and rare. Common fragile sites are expressed in all individuals at different frequencies, whereas rare ones are found only in certain individuals. Common and rare fragile sites have been shown to display a number of characteristics of instability being preferential sites for chromosomal deletions, duplications', and rearrangements. Moreover, a majority of mapped oncogenes are located at or near these fragile sites. These observations have led to the suggestion that both classes of fragile sites may play a significant role in chromosomal rearrangements involved in oncogene activation or tumor supressor gene inactivation. For these reasons, involvement of common and rare fragile sites and their relevance to specific chromosome breakpoints in cancer have received much attention. In this study, which reports on the cytogenetic findings obtained from 256 patients with chronic myelocytic leukemia, 103 with acute myelocytic leukemia, 40 with acute lymphocytic leukemia, 33 with myelodysplastic syndrome, we documented the fragile sites involved in chromosomal aberrations involving oncogenes, tumor supressor genes, and other known genes important in cell cycle regulation localized at these sites. (C) 2002 Elsevier Science Inc. All rights reserved.