Microsatellite alterations in serum DNA of head and neck cancer patients

Microsatellite alterations in serum DNA of head and neck cancer patients
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DOI:
10.1038/nm0996-1035
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发表时间:
1996-09-01
期刊:
影响因子:
82.9
通讯作者:
Sidransky, D
Sidransky, D
中科院分区:
医学1区
文献类型:
--
作者:
Nawroz, H;Koch, W;Sidransky, D

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微卫星DNA改变是肿瘤进展的一个组成部分,并且作为检测人类癌症的克隆标记物是有价值的(1-3)。此外,最近的证据表明,衰老的肿瘤细胞可能会释放DNA进入循环,随后由血清和血浆携带,因此在血清和血浆中富集(4,5)。我们检测了21例原发性头颈部鳞状细胞癌(HNSCC)患者的淋巴细胞和配对血清样本的DNA聚合酶链反应(PCR)为基础的微卫星分析。根据血清中12个标记物中每一个的新等位基因(移位)或杂合性缺失(洛)的存在,对患者的改变进行评分,然后与原发肿瘤DNA进行比较。21例患者中有6例(29%)发现血清中有一个或多个微卫星改变,与原发性肿瘤中的微卫星改变精确匹配。所有6例患者均为晚期疾病(III期或IV期);其中5例患者有淋巴结转移,3例后来发生远处转移,4例死于疾病。血清微卫星分析是检测循环肿瘤细胞DNA的一种新方法。如果这些结果在更大规模的研究中得到证实,微卫星标记物可能有助于评估癌症患者的肿瘤负荷。
Microsatellite DNA alterations are an integral part of neoplastic progression and are valuable as clonal markers for the detection of human cancers(1-3). Moreover, recent evidence suggests that senescent tumor cells may release DNA into the circulation, which is subsequently carried by and therefore enriched in the serum and plasma(4,5). We tested 21 patients with primary head and neck squamous cell carcinoma (HNSCC) by polymerase chain reaction (PCR)-based microsatellite analysis of DNA from lymphocytes and paired serum samples. Patients were scored for alterations as defined by the presence of new alleles (shifts) or loss of heterozygosity (LOH) in serum at each of 12 markers and then compared with primary tumor DNA. Six out of 21 patients (29%) were found to have one or more microsatellite alterations in serum precisely matching those in the primary tumors. All six patients had advanced disease (stage III or IV); five of these patients had nodal metastases, three later developed distant metastases, and four died of disease. Microsatellite analysis of serum represents a novel method for the detection of circulating tumor cell DNA. If these results are confirmed in larger studies, microsatellite markers may be useful in assessing tumor burden in cancer patients.