Frequency of RAS gene mutation and its cooperative genetic events in Southeast Asian adult acute myeloid leukemia
Frequency of RAS gene mutation and its cooperative genetic events in Southeast Asian adult acute myeloid leukemia
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DOI：
10.1111/j.1600-0609.2006.00663.x
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发表时间：
2006-07-01
影响因子：
3.1
通讯作者：
Tocharoentanaphol, Chintana
中科院分区：
文献类型：
--
作者：
Auewarakul, Chirayu U.;Lauhakirti, Darat;Tocharoentanaphol, Chintana
RAS基因作为急性髓系白血病（AML）中最常见的突变基因之一，已成为分子治疗的一个重要靶点。致癌RAS及其相关遗传事件在AML中的作用尚未确定。我们使用聚合酶链反应-单链构象多态性分析检测了239例泰国初治成人AML患者的RAS突变频率。在32例（13%）病例中发现了35个RAS突变，主要分类为M1/M2（53%），其次是M4/M5亚型（38%）。N-RAS密码子12阳性10例，N-RAS密码子61阳性11例，N-RAS密码子13阳性13例，K-RAS密码子13阳性1例。未发现K-RAS外显子2或H-RAS突变。最常见的碱基替换是密码子13处的G到A的转变。大多数M1/M2病例在密码子12或13处发生突变，而M4/M5病例优先影响密码子61。一半的RAS突变患者有异常核型，大多数涉及染色体21，11和7。4例患者患有核心结合因子白血病，另外4例患者同时存在FLT3或AML 1突变。1例患者有RAS、FLT3和t（8; 21），另1例患者有RAS、AML 1点突变和del（9q）。总之，RAS基因突变在泰国人中并不像在西方人群中那样常见。在RAS突变的患者中发生了几种额外的遗传异常。未来的分子靶向方法应考虑AML患者中与RAS突变共存的多种遗传事件。
RAS gene as one of the most frequently mutated genes in acute myeloid leukemia (AML) has become an attractive target for molecular therapy. The role of oncogenic RAS and its associated genetic events in AML are not yet defined. We examined the frequency of RAS mutation in 239 Thai de novo adult AML patients using polymerase chain reaction-single-strand conformational polymorphism analysis. Thirty-five RAS mutations were found in 32 cases (13%) predominantly classified as M1/M2 (53%) followed by M4/M5 subtype (38%). Ten cases were positive for N-RAS codon 12, 11 cases for N-RAS codon 61, 13 cases for N-RAS codon 13, and one case for K-RAS codon 13. No mutation was found in K-RAS exon 2 or H-RAS. The most common base substitution was the G to A transition at codon 13. Most M1/M2 cases had mutations at codon 12 or 13, whereas M4/M5 cases preferentially affected codon 61. Half of the patients with RAS mutations had abnormal karyotypes with the majority involving chromosomes 21, 11 and 7. Four patients had core-binding factor leukemia and four additional patients had coexisting FLT3 or AML1 mutation. One patient had RAS, FLT3 and t(8;21) and the other had RAS, AML1 point mutation and del(9q). In conclusion, mutation of RAS gene was not as common in the Thais as in the western population. Several additional genetic abnormalities occurred in RAS-mutated patients. Future molecular-targeting approaches should take into account the multiple genetic events that coexist with RAS mutations in AML patients.