脆性基因FHIT与WWOX在白血病中的表达

Expression of Fragile Genes WWOX and FHIT in Leukemia

普通染色体脆性位点是在弱小的DNA复制压力下表现出来的,用缺口或溢痕来形容的特定的细胞遗传学条带,它们在癌症中有频繁的改变。其中FRA3B位点中的脆性组氨酸三联体基因与FRA16D位点中的WW域的氧化还原酶基因是目前研究最多的脆性基因,它们在多种上皮性肿瘤中改变并呈现出肿瘤抑制作用。这两个基因的改变由启动子区域异常甲基化及组蛋白修饰、等位基因缺失以及mRNA异常拼接造成。原发性白血病中也存在这两个基因表达的改变。因此,普通脆性位点基因的改变可能参与了白血病的临床病理过程。

Common chromosomal fragile sites are ex-pressed as gaps or constrictions at specific cytogenetic bands under the condition of mild DNA replication stress,and they are frequently altered in cancer.Among these,FHIT gene at FRA3B and WWOX gene at FRA16D are researched frequently,and they are altered in various epithelial tumors and exhibit tumor suppressor function.Researches shows alterations of these two fragile genes are resulted from methylation and histone modification,alletic loss and aberrantly spliced forms of gene mRNA.Aberration of FHIT and WWOX expression recently were detected in primary leukemia.Thus gene alterations at common fragile sites are involved in clinicopathological outcomes of primary leukemia.