Research and Development, SRL Ltd, Mumbai, India.
Histopathology Division, SRL Ltd, Mumbai, India.
Cancer Rep (Hoboken). 2018 Oct;1(3):e1130. doi: 10.1002/cnr2.1130. Epub 2018 Sep 17.
Molecular alteration of FGFR3 gene is the most common genetic event currently known in bladder cancer. Notably, FGFR3 mutation has emerged as a promising molecular biomarker for recurrence, prognosis, and therapeutic target in bladder cancer.
The present study explored the frequency and distribution pattern of FGFR3 mutation in 100 Indian bladder cancer patients.
Exons 7, 10, and 15 were subjected to nested PCR followed by bidirectional sequencing of the PCR products. Overall, FGFR3 gene mutations were identified in 19 bladder cancer patients (19%, 19 of 100). Most of the mutations were noted in exon 7 (15%), followed by exon 10 (4%). All mutations detected were missense in nature affecting amino acids at codons 248, 249, and 373. The S249C mutations were the most recurrent mutation seen in exon 7, while Y373C was commonly observed in exon 10. In contrast to exons 7 and 10, no mutations were seen in exon 15 in this study. Females and older age patients tend to show increased frequency of FGFR3 mutations. Furthermore, FGFR3 mutations were more common in low pathological stage (6/20 pTa and 13/71 pT1) and low-grade tumors (13/46). This predominance in low-grade tumors were significantly high in comparison to high-grade tumor (P = .04). Likewise, FGFR3 mutations were significantly higher in well-differentiated tumors (32.6%, 14/43) in comparison to moderately differentiated tumors (11.3%, 5/44), and poorly differentiated tumor (0%, 0/13) (P = .007). No other association of FGFR3 with tumor size, necrosis, and variant histology was noted.
The current study highlights the spectrum of FGFR3 mutation in Indian patients, and the data presented here are similar to those reported from across the globe.
FGFR3 基因的分子改变是目前膀胱癌中最常见的遗传事件。值得注意的是，FGFR3 突变已成为膀胱癌复发、预后和治疗靶点的有前途的分子生物标志物。
本研究探讨了 100 例印度膀胱癌患者中 FGFR3 突变的频率和分布模式。
对第 7、10 和 15 外显子进行巢式 PCR，然后对 PCR 产物进行双向测序。总体而言，在 19 例膀胱癌患者（19%，100 例中的 19 例）中发现 FGFR3 基因突变。大多数突变发生在第 7 外显子（15%），其次是第 10 外显子（4%）。所有检测到的突变均为错义突变，影响密码子 248、249 和 373 处的氨基酸。第 7 外显子中最常见的突变是 S249C 突变，第 10 外显子中常见的是 Y373C 突变。与第 7 和 10 外显子不同，本研究中在第 15 外显子中未发现突变。女性和老年患者 FGFR3 突变频率较高。此外，FGFR3 突变在低病理分期（6/20 pTa 和 13/71 pT1）和低级别肿瘤（13/46）中更为常见。与高级别肿瘤相比，这种在低级别肿瘤中的优势非常显著（P=0.04）。同样，在分化良好的肿瘤（32.6%，14/43）中 FGFR3 突变明显高于中分化肿瘤（11.3%，5/44）和低分化肿瘤（0%，0/13）（P=0.007）。未观察到 FGFR3 与肿瘤大小、坏死和变异组织学之间的其他关联。
本研究强调了印度患者 FGFR3 突变的谱，这里提供的数据与全球报道的数据相似。
