Smal M P, Rolevich A I, Polyakov S L, Krasny S A, Goncharova R I
Institute of Genetics and Cytology, National Academy of Sciences of Belarus, Minsk 20072, Republic of Belarus.
N.N. Alexandrov National Cancer Center of Belarus, Department of Urology, Minsk 223040, Republic of Belarus.
Exp Oncol. 2014 Dec;36(4):246-51.
The aim of this study was to determine the frequencies of FGFR3 and TP53 mutations in a prospective cohort of 150 bladder cancer patients and to assess the relationship between their mutational status and clinicopathological variables.
The FGFR3 and TP53 mutations were detected by the SNaPshot method and PCR-single-strand conformational polymorphism analysis followed by DNA sequencing.
The activating FGFR3 mutations were found in 71 (47.3%) whereas TP53 mutations were observed in 31 (20.7%) urothelial carcinomas. FGFR3-mutant tumors significantly correlated with lower tumor stage and grade, papillary form of bladder cancer and the absence of metastases while TP53-mutant tumors were strongly associated with higher tumor stage and grade as well as the presence of metastasis. We also found significant inverse correlation between FGFR3 mutations and TP53 alterations in urothelial carcinomas (p=0.03). Four possible genotypes were observed in the whole studied cohort, namely FGFR3mut/TP53wt (41.3%), FGFR3wt/TP53wt (38%), FGFR3wt/TP53mut (14.7%), and FGFR3mut/TP53mut (6%). Tumors with FGFR3wt/TP53wt genotype comprised the subgroup, in which all stages and grades were equally distributed.
Our findings confirm the alternative role of FGFR3 and TP53 mutations in the development of bladder cancer. Together these two genetic markers are attributed to 62% of the tumors studied. Tumors with both wild type genes included urothelial carcinomas of all stages and grades and may develop through another genetic pathway. To elucidate complete molecular profile of bladder tumors further additional studies are needed.
本研究旨在确定150例膀胱癌患者前瞻性队列中FGFR3和TP53突变的频率，并评估其突变状态与临床病理变量之间的关系。
采用SNaPshot方法及PCR-单链构象多态性分析并结合DNA测序检测FGFR3和TP53突变。
在71例（47.3%）尿路上皮癌中发现激活型FGFR3突变，而在31例（20.7%）中观察到TP53突变。FGFR3突变型肿瘤与较低的肿瘤分期和分级、膀胱癌的乳头状形态以及无转移显著相关，而TP53突变型肿瘤与较高的肿瘤分期和分级以及转移的存在密切相关。我们还发现尿路上皮癌中FGFR3突变与TP53改变之间存在显著的负相关（p=0.03）。在整个研究队列中观察到四种可能的基因型，即FGFR3mut/TP53wt（41.3%）、FGFR3wt/TP53wt（38%）、FGFR3wt/TP53mut（14.7%）和FGFR3mut/TP53mut（6%）。具有FGFR3wt/TP53wt基因型的肿瘤构成一个亚组，其中所有分期和分级分布均匀。
我们的研究结果证实了FGFR3和TP53突变在膀胱癌发生发展中的替代作用。这两个基因标记共同占所研究肿瘤的62%。具有两种野生型基因的肿瘤包括所有分期和分级的尿路上皮癌，可能通过另一种遗传途径发展。为阐明膀胱肿瘤的完整分子谱，还需要进一步的研究。
