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[5号染色体长臂(5q21)杂合性缺失在肺小细胞癌中的意义]

[Significance of heterozygosity loss in the long arm of chromosome 5 (5q21) in small cell carcinoma of the lung].

作者信息

Sánchez Céspedes M, López Cabrerizo M P, Moreno I, Ariza A, Monzó M, Rosell R

机构信息

Laboratorio de Biologia Molecular del Cáncer, Hospital Germans Trias i Pujol, Badalona, Barcelona.

出版信息

Med Clin (Barc). 1997 May 31;109(1):1-5.

PMID:9303970
Abstract

BACKGROUND

Loss of heterozygosity (LOH) at 5q21, where the APC/MCC genes reside, is one of the genetic alterations that characterizes lung cancer. The aim of this study was to analyse LOH frequency on chromosome 5q21 in patients with non-small cell lung cancer and its relationship with TNM staging and histological subtypes.

PATIENTS AND METHODS

Tumor and corresponding normal DNA were isolated from 60 patients with non-small cell lung cancer and a subsequent polymerase chain reaction (PCR) with microsatellite markets within the APC/MCC region was performed. The PCR products were resolved by electrophoresis. The comparison between the normal and tumor DNA patterns allowed us to detect the samples harboring LOH.

RESULTS

LOH at 5q21 was detected in 20% of the patients. LOH at 5q21 was found in 16% of stage I patients, 8% in stage II patients and 40% in stage IIIA patients. A trend towards worse survival was detected in stage IIIA patients with LOH at 5q21 (9 months median time survival) in comparison with patients with LOH (21 months), although the difference was not statistically significant (p = 0.11). No significant differences in LOH were observed among histological types. In addition, we found no correlation between LOH and higher frequency of mutations rate affecting K-ras and p53 genes.

CONCLUSIONS

LOH at 5q21 is a frequent genetic alteration in non-small cell lung cancer and correlates with locally advanced disease (stage IIIA). Our results suggest that LOH at the 5q21 region could be a prognostic factor in non-small cell lung cancer.

摘要

背景

5q21区域存在杂合性缺失(LOH),而APC/MCC基因位于该区域,这是肺癌的特征性基因改变之一。本研究的目的是分析非小细胞肺癌患者5号染色体q21区域的LOH频率及其与TNM分期和组织学亚型的关系。

患者与方法

从60例非小细胞肺癌患者中分离肿瘤及相应的正常DNA,随后在APC/MCC区域内使用微卫星标记进行聚合酶链反应(PCR)。PCR产物通过电泳进行分离。通过比较正常和肿瘤DNA图谱,我们能够检测出存在LOH的样本。

结果

20%的患者检测到5q21区域存在LOH。在I期患者中,5q21区域存在LOH的比例为16%,II期患者中为8%,IIIA期患者中为40%。与不存在LOH的患者(中位生存时间21个月)相比,IIIA期存在5q21区域LOH的患者生存趋势较差(中位生存时间9个月),尽管差异无统计学意义(p = 0.11)。在不同组织学类型之间,未观察到LOH存在显著差异。此外,我们发现LOH与影响K-ras和p53基因的较高突变率之间没有相关性。

结论

5q21区域的LOH是非小细胞肺癌中常见的基因改变,并且与局部晚期疾病(IIIA期)相关。我们的结果表明,5q21区域的LOH可能是非小细胞肺癌的一个预后因素。

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