ANALYSIS OF RAS GENE-MUTATIONS IN ACUTE MYELOID-LEUKEMIA BY POLYMERASE CHAIN-REACTION AND OLIGONUCLEOTIDE PROBES
ANALYSIS OF RAS GENE-MUTATIONS IN ACUTE MYELOID-LEUKEMIA BY POLYMERASE CHAIN-REACTION AND OLIGONUCLEOTIDE PROBES
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DOI：
10.1073/pnas.85.5.1629
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发表时间：
1988-03-01
影响因子：
11.1
通讯作者：
MARSHALL, CJ
中科院分区：
文献类型：
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作者：
FARR, CJ;SAIKI, RK;MARSHALL, CJ
采用体外DNA扩增和寡核苷酸点印迹法研究急性髓性白血病（AML）中RAS基因的突变。筛选了52种呈状AML dna，检测NRAS密码子12、13和61以及KRAS和HRAS密码子12和61的突变。14个（27%）包含突变——全部在NRAS中，主要在密码子12中。最常见的氨基酸取代是在密码子12（7/18）上被天冬氨酸取代，具有G .fwdarw。过渡是最常见的碱基变化（11/18）。疾病亚型与NRAS突变的发生率或类型之间没有特别的相关性。在4例患者的DNA样本中，发现2种NRAS突变共存。NIH 3T3聚焦形成试验显示，在每种病例中，突变存在于不同的NRAS等位基因中。我们还报道了在四位患者的复发dna中缺乏突变的RAS基因，其中在出现时检测到RAS癌基因。这些观察结果表明，RAS突变是肿瘤转化进化的一部分。
In vitro DNA amplification followed by oligonucleotide dot blot analysis were used to study RAS gene mutations in acute myeloid leukemia (AML). Fifty-two presentation AML DNAs were screened for mutation in codons 12, 13, and 61 of NRAS and in codons 12 and 61 of KRAS and HRAS. Fourteen (27%) contained mutations-all in NRAS and predominantly in codon 12. The most common amino acid substitution identified was of glycine by aspartic acid at codon 12 (7/18), with a G .fwdarw. A transition being the most common base change (11/18). No particular correlation was observed between disease subtype and the incidence or type of NRAS mutation. In DNA samples from four patients, 2 NRAS mutations were found to coexist. NIH 3T3 focus-formation assays revealed that in each case the mutations were present in different NRAS alleles. We also report the absence of a mutated RAS gene in relapse DNAs of four patients in which a RAS oncogene had been detected at presentation. These observations suggest that RAS mutations arise as part of the evolution of neoplastic transformation.