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FGFR3 and Ras gene mutations are mutually exclusive genetic events in urothelial cell carcinoma

机译：FGFR3和Ras基因突变是尿路上皮细胞癌的互斥遗传事件

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Fibroblast growth factor receptor 3 (FGFR3) mutations are frequent in superficial urothelial cell carcinoma (UCC). Ras gene mutations are also found in UCC. As oncogenic activation of both FGFR3 and Ras is predicted to result in stimulation of the mitogen-activated protein kinase (MAPK) pathway, we hypothesized that these might be mutually exclusive events. HRAS mutation has been widely studied in UCC, but all three Ras gene family members have not been screened for mutation in the same sample series. We screened 98 bladder tumours and 31 bladder cell lines for mutations in FGFR3, HRAS, NRAS and KRAS2. FGFR3 mutations were present in 54 tumours (55%) and three cell lines (10%), and Ras gene mutations in 13 tumours (13%) and four cell lines (13%). These included mutations in all three Ras genes; ten in HRAS, four in KRAS2 and four in NRAS and these were not associated with either tumour grade or stage. In no cases were Ras and FGFR3 mutation found together. This mutual exclusion suggests that FGFR3 and Ras gene mutation may represent alternative means to confer the same phenotype on UCC cells. If these events have biological equivalence, Ras mutant invasive UCC may represent a novel subgroup.
机译：成纤维细胞生长因子受体3（FGFR3）突变在浅层尿路上皮细胞癌（UCC）中很常见。在UCC中也发现了Ras基因突变。由于FGFR3和Ras的致癌激活预计会导致促有丝分裂原激活的蛋白激酶（MAPK）通路的刺激，我们假设这些可能是相互排斥的事件。 HRAS突变已在UCC中进行了广泛研究，但是尚未在同一样品系列中对所有三个Ras基因家族成员进行突变筛查。我们筛选了98个膀胱肿瘤和31个膀胱细胞系中FGFR3，HRAS，NRAS和KRAS2中的突变。 FGFR3突变存在于54个肿瘤（55％）和三个细胞系（10％）中，而Ras基因突变存在于13个肿瘤（13％）和四个细胞系中（13％）。其中包括所有三个Ras基因的突变; HRAS中有10例，KRAS2中有4例，NRAS中有4例，它们与肿瘤的分级或分期无关。在任何情况下都不会同时发现Ras和FGFR3突变。这种相互排斥表明，FGFR3和Ras基因突变可能代表了在UCC细胞上赋予相同表型的替代方法。如果这些事件具有生物学等效性，则Ras突变型浸润性UCC可能代表一个新的亚组。

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