Smardova Jana, Liskova Kvetoslava, Ravcukova Barbora, Malcikova Jitka, Hausnerova Jitka, Svitakova Miluse, Hrabalkova Renata, Zlamalikova Lenka, Stano-Kozubik Katerina, Blahakova Ivona, Speldova Jana, Jarkovsky Jiri, Smarda Jan
Department of Pathology, University Hospital, Brno, Czech Republic.
Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic.
Oncol Rep. 2016 Mar;35(3):1859-67. doi: 10.3892/or.2015.4533. Epub 2015 Dec 29.
Lung cancer is the leading cause of cancer-related deaths worldwide. The p53 tumor suppressor is a transcription factor controlling expression of its target genes in response to various stress stimuli. Mutations of the TP53 gene occur very frequently in lung carcinomas and they play an important role in both oncogenic transformation of lung epithelial cells and lung carcinoma progression. We determined the TP53 status in 42 samples of squamous cell lung carcinoma (SQCC) and 56 samples of lung adenocarcinoma (AC) by the functional analysis FASAY and its variant called split assay. Altogether, we detected 64 TP53 mutations in 63 patients and analyzed them by cDNA and gDNA sequencing. The TP53 mutations were found in 76.2% (32/42) of SQCC cases, and 55.4% (31/56) of ACs. Immunoblotting revealed the p53 protein accumulation in 18 samples (42.9%) among SQCC cases and 19 samples (33.9%) among AC cases. Using fluorescence in situ hybridization we detected loss of the TP53-specific 17p13.3 locus in 23 from 41 analyzed SQCC samples (56.1%) and in 20 from 54 analyzed AC samples (37.0%). We did not find any statistically significant differences in overall and disease-free survival in relation to TP53 status.
肺癌是全球癌症相关死亡的主要原因。p53肿瘤抑制因子是一种转录因子，可响应各种应激刺激来控制其靶基因的表达。TP53基因的突变在肺癌中非常频繁地发生，它们在肺上皮细胞的致癌转化和肺癌进展中均起重要作用。我们通过功能分析FASAY及其变体分裂分析确定了42例肺鳞状细胞癌（SQCC）样本和56例肺腺癌（AC）样本中的TP53状态。我们共在63例患者中检测到64个TP53突变，并通过cDNA和gDNA测序对其进行了分析。在76.2%（32/42）的SQCC病例和55.4%（31/56）的AC病例中发现了TP53突变。免疫印迹显示，SQCC病例中有18个样本（42.9%）和AC病例中有19个样本（33.9%）存在p53蛋白积累。使用荧光原位杂交，我们在41个分析的SQCC样本中有23个（56.1%）以及在54个分析的AC样本中有20个（37.0%）检测到TP53特异性的17p13.3位点缺失。我们未发现与TP53状态相关的总生存期和无病生存期存在任何统计学上的显著差异。
