Presence of a p53 gene deletion in patients with multiple myeloma predicts for short survival after conventional-dose chemotherapy
Presence of a p53 gene deletion in patients with multiple myeloma predicts for short survival after conventional-dose chemotherapy
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DOI：
10.1182/blood.v92.3.802.415a17_802_809
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发表时间：
1998-08-01
期刊：
影响因子：
20.3
通讯作者：
Huber, H
中科院分区：
文献类型：
--
作者：
Drach, J;Ackermann, J;Huber, H
(I)n对于多发性骨髓瘤（MM），先前的研究表明，p53基因突变在新诊断疾病的患者中是罕见事件，但不知道p53缺失在MM中是否具有任何意义。为了解决这个问题，我们使用间期荧光原位杂交（FISH）用特异于17 p13处p53基因座的DNA探针，研究了72例MM患者的骨髓浆细胞（59例患者= 81.9%治疗前）。通过FISH，发现主要是单等位基因的p53缺失分别在32.8%和54.5%的新诊断和复发MM患者中检测到。6例p53基因缺失的患者的染色体核型显示，其中只有1例存在17 p的结构异常。包括远端17 p探针（D17 S34位点特异性）在内的其他FISH研究提供了17 p间质缺失导致骨髓瘤细胞中p53杂交信号丢失的证据。在所有59例新诊断的MM患者中，p53缺失与III期相关（P = 0.054），但与其他实验室和临床参数无关。p53基因缺失患者的生存时间明显短于未缺失患者，两者均从诊断时算起[中位数13.9 v38.7个月; P
(I)n multiple myeloma (MM), previous studies showed that mutations of the p53 gene are rare events in patients with newly diagnosed disease, but it is not known whether deletions of p53 are of any significance in MM. To address this question, we used interphase fluorescence in situ hybridization (FISH) with a DNA probe specific for the p53 locus at 17p13 and investigated bone marrow plasma cells from 72 patients with MM (59 patients = 81.9% before therapy). By FISH, deletions of p53, which were found to be predominantly monoallelic, were detected in 32.8% and 54.5% of patients with newly diagnosed and relapsed MM, respectively. Karyotypes from six of the patients with a p53 deletion by FISH showed a structural abnormality of 17p in only one of them. Additional FISH studies including a distal-17p probe (specific for the D17S34 locus) provided evidence for an interstitial deletion on 17p resulting in loss of p53 hybridization signals in myeloma cells. Among all 59 patients with newly diagnosed MM, presence of a p53 deletion was associated with stage III (P =.054), but not with other laboratory and clinical parameters. Patients with a p53 deletion had significantly shorter survival time compared with those without a deletion, both from the time of diagnosis [median 13.9 v38.7 months; P