Institute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA.
Leukemia. 2011 Jan;25(1):130-4. doi: 10.1038/leu.2010.247. Epub 2010 Oct 29.
Loss of function mutations and deletions encompassing the plant homeodomain finger 6 (PHF6) gene are present in about 20% of T-cell acute lymphoblastic leukemias (ALLs). Here, we report the identification of recurrent mutations in PHF6 in 10/353 adult acute myeloid leukemias (AMLs). Genetic lesions in PHF6 found in AMLs are frameshift and nonsense mutations distributed through the gene or point mutations involving the second plant homeodomain (PHD)-like domain of the protein. As in the case of T-ALL, where PHF6 alterations are found almost exclusively in males, mutations in PHF6 were seven times more prevalent in males than in females with AML. Overall, these results identify PHF6 as a tumor suppressor gene mutated in AML and extend the role of this X-linked tumor suppressor gene in the pathogenesis of hematologic tumors.
丧失功能的突变和缺失包含植物 homeodomain 指 6 （PHF6）基因存在于约 20%的 T 细胞急性淋巴细胞白血病（ALL）。在这里，我们报告在 353 例成人急性髓细胞白血病（AML）中发现 PHF6 反复出现的突变。在 AML 中发现的 PHF6 遗传病变是通过基因分布的移码和无义突变或涉及蛋白质第二植物 homeodomain（PHD）样结构域的点突变。与 T-ALL 情况一样，在那里 PHF6 改变几乎只发生在男性中，AML 中 PHF6 的突变在男性中比女性中更为常见，大约是女性的 7 倍。总的来说，这些结果表明 PHF6 是 AML 中突变的肿瘤抑制基因，并扩展了这个 X 连锁肿瘤抑制基因在血液肿瘤发病机制中的作用。
