Sánchez-Céspedes M, Rosell R, Pifarré A, López-Cabrerizo M P, Barnadas A, Sánchez J J, Lorenzo J C, Abad A, Monzó M, Navas-Palacios J J
Laboratory of Molecular Biology of Cancer, Medical Oncology Service, Universitat Autónoma de Barcelona, Crtra Canyet s/n, 08916 Badalona, Spain.
Clin Cancer Res. 1997 Jul;3(7):1229-35.
We investigated the clinical implications of allelic deletions at three common sites of loss of heterozygosity (LOH) in regions 5q21, 11p15.5, and 11p13 in 86 patients with non-small cell lung cancer (NSCLC). We performed a PCR-based microsatellite polymorphism assay for detection of LOH. The microsatellite markers used were D5S82 (proximal to the APC gene), MCC (within the MCC gene), D11S904 (11p13), HRAS (within the H-ras gene), and D11S860 (11p15.5). Of the 68 informative cases at 5q21 loci, LOH was found in 14 cases (20%), whereas LOH frequency in 11p15.5 and 11p13 was 31% (19 of 61 informative cases) and 19% (12 of 63 informative cases), respectively. There was a significant correlation between 5q21 LOH and mediastinal lymph node involvement (P = 0.03). However, no differences were observed in median survival times (26 months in patients with 5q21 LOH versus 37 months in the remainder; P = 0.33) nor in patients with 11p LOH (38 months versus 32 months, respectively; P = 0.72). Cox's proportional hazards model predicted that stage was the only independent poor prognostic marker in the entire cohort of NSCLC patients. Thus, the present study revealed two important abnormalities, LOH at chromosome 5q21 and LOH at chromosome 11p, both implied in NSCLC development.
我们研究了86例非小细胞肺癌(NSCLC)患者在5q21、11p15.5和11p13区域三个常见杂合性缺失(LOH)位点的等位基因缺失的临床意义。我们进行了基于聚合酶链反应(PCR)的微卫星多态性分析以检测LOH。所用的微卫星标记为D5S82(靠近APC基因)、MCC(在MCC基因内)、D11S904(11p13)、HRAS(在H-ras基因内)和D11S860(11p15.5)。在5q21位点的68例信息性病例中,14例(20%)发现有LOH,而11p15.5和11p13的LOH频率分别为31%(61例信息性病例中的19例)和19%(63例信息性病例中的12例)。5q21 LOH与纵隔淋巴结受累之间存在显著相关性(P = 0.03)。然而,在中位生存时间方面未观察到差异(5q21 LOH患者为26个月,其余患者为37个月;P = 0.33),11p LOH患者也未观察到差异(分别为38个月和32个月;P = 0.72)。Cox比例风险模型预测,分期是整个NSCLC患者队列中唯一的独立不良预后标志物。因此,本研究揭示了两个重要异常,即5号染色体q21区域的LOH和11号染色体p区域的LOH,二者均与NSCLC的发生有关。