ANALYSIS OF RAS ONCOGENE MUTATIONS IN HUMAN LYMPHOID MALIGNANCIES
ANALYSIS OF RAS ONCOGENE MUTATIONS IN HUMAN LYMPHOID MALIGNANCIES
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DOI：
10.1073/pnas.85.23.9268
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发表时间：
1988-12-01
影响因子：
11.1
通讯作者：
DALLAFAVERA, R
中科院分区：
文献类型：
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作者：
NERI, A;KNOWLES, DM;DALLAFAVERA, R
我们研究了人类淋巴系统恶性肿瘤中激活RAS癌基因的突变频率，包括B和T细胞源性急性淋巴细胞白血病、慢性淋巴细胞白血病和非霍奇金淋巴瘤。应用聚合酶链反应/寡核苷酸杂交技术检测178例HRAS、KRAS、NRAS基因第12、61位密码子和NRAS基因第13位密码子的激活突变。33例急性淋巴细胞白血病中有6例（6/33，18%）发现NRAS基因第12或13密码子突变，而非霍奇金淋巴瘤和慢性淋巴细胞白血病中未发现突变。聚合酶链反应产物的直接核苷酸序列分析表明，突变涉及一个G fwdar。6例急性淋巴细胞白血病中5例的转化。在4例病例中，突变似乎仅发生在一部分肿瘤细胞中，1例病例显示两种不同的NRAS突变，最有可能存在于两种不同的细胞群中。这些结果表明：（i）RAS癌基因并不存在于所有类型的人类恶性肿瘤中，（ii）RAS突变频率的显著差异可以在来源于相同组织的肿瘤亚型中发现，（iii）在淋巴肿瘤中，NRAS突变与大多数未分化的急性淋巴细胞白血病表型相关，和（iv）仅存在于一部分恶性细胞中的NRAS突变可能是由于肿瘤发展过程中突变等位基因的选择性丢失或获得。
We investigated the frequency of mutations activating RAS oncogenes in human lymphoid malignancies, including B- and T-cell-derived acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. By the polymerase chain reaction/oligonucleotide hybridization method, DNA from 178 cases was analyzed for activating mutations involving codons 12 and 61 of the HRAS, KRAS and NRAS genes and codon 13 of the NRAS gene. Mutations involving codons 12 or 13 of the NRAS gene were detected in 6 of 33 cases of acute lymphoblastic leukemia (6/33, 18%), whereas no mutations were found in non-Hodgkin lymphoma or chronic lymphocytic leukemia. Direct nucleotide sequence analysis of polymerase chain reaction products showed that the mutations involved a G .fwdarw. A transition in five of the six cases of acute lymphocytic leukemia. In four cases the mutations seemed to occur in only a fraction of the neoplastic cells, and one case displayed two distinct NRAS mutations, most likely present in two distinct cell populations. These results indicate the following: (i) RAS oncogenes are not found in all types of human malignancies, (ii) significant differences in the frequency of RAS mutations can be found among subtypes of neoplasms derived from the same tissue, (iii) in lymphoid neoplasms the NRAS mutation correlates with the most undifferentiated acute lymphocytic leukemia phenotype, and (iv) NRAS mutations present in only a fraction of malignant cells may result from either the selective loss or the acquisition of mutated alleles during tumor development.