Activating mutations of N- and K-ras in multiple myeloma show different clinical associations: Analysis of the Eastern Cooperative Oncology Group phase III trial
Activating mutations of N- and K-ras in multiple myeloma show different clinical associations: Analysis of the Eastern Cooperative Oncology Group phase III trial
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DOI：
10.1182/blood.v88.7.2699.bloodjournal8872699
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发表时间：
1996-10-01
期刊：
影响因子：
20.3
通讯作者：
VanNess, B
中科院分区：
文献类型：
--
作者：
Liu, PC;Leong, T;VanNess, B
ras家族成员突变是多发性骨髓瘤（MM）中最常见的癌基因突变。我们检查了参加东部肿瘤协作组（ECOG）III期临床试验E9486的160名新诊断MM患者中密码子12、13和61处N-和K-ras基因的突变状态。MS突变的总发生率被发现是39%的样本分析。5名患者显示出一种以上突变的证据。我们从疾病进展或复发的患者中获得了22份骨髓样本，这些患者在诊断时就发现了ms突变。在所有病例中，疾病进展样本的res突变与诊断时发现的相同。相反，25名在诊断时没有表现出任何ms突变的患者中有3名在疾病进展时获得了res突变。ras基因突变与疾病分期、β 2-微球蛋白水平之间无显著相关性。标记指数或蛋白质类型。N-ras基因突变患者的平均肿瘤负荷和中位生存期与无ras基因突变患者无明显区别。然而，K-ras基因突变的患者在诊断时的平均骨髓肿瘤负荷显著高于无ras基因突变的患者（57% vs36%，P
Mutations of members of the ras family are among the most common oncogene mutations found in multiple myeloma (MM). We have examined the mutational status of the N- and K-ras genes at codons 12, 13, and 61 in 160 newly diagnosed MM patients enrolled on the Eastern Cooperative Oncology Group (ECOG) phase III clinical trial E9486. The total incidence of ms mutations was found to be 39% of the samples analyzed. Five patients showed evidence of more than one mutation. We obtained 22 marrow samples from patients at the time of disease progression or relapse, for whom a ms mutation was identified at diagnosis. In all cases, the res mutation of the disease progression sample was identical to that found at diagnosis. In contrast, three of 25 patients who did not show any ms mutation at diagnosis acquired a res mutation at the time of disease progression. No significant association was observed between any ras mutation and stage of disease, beta(2)-microglobulin levels. labeling index, or protein type. The mean tumor burden and median survival for patients with mutations of N-ras was indistinguishable from patients with no ras mutations. However, patients with K-ras mutations had a significantly higher mean bone marrow tumor burden at diagnosis than patients with no ras mutations (57% v 36%, P