Kimura T, Suzuki H, Ohashi T, Asano K, Kiyota H, Eto Y
Department of Urology, Institute of DNA Medicine, Jikei University, School of Medicine, Tokyo, Japan.
Cancer. 2001 Nov 15;92(10):2555-61. doi: 10.1002/1097-0142(20011115)92:10<2555::aid-cncr1607>3.0.co;2-m.
The point mutations of fibroblast growth factor receptor 3 (FGFR3) are associated with autosomal dominant human skeletal disorders such as thanatophoric dysplasia (TD). However, point mutations were reported in a small series of bladder carcinomas, suggesting their oncogenic role. In view of these findings, the authors investigated the incidence of TD mutations in the FGFR3 gene in a large series of bladder carcinomas to clarify their role in the progression of bladder carcinoma.
Specimens of transitional cell carcinoma of the urinary bladder from 81 patients were screened for the FGFR3 mutations (codons 248, 249, 372, 373, 375, 652, 809) that have been reported in TD, using polymerase chain reaction-restriction fragment length polymorphism, single-strand conformation polymorphism, and DNA sequencing.
Point mutations were detected in 25 of 81 carcinomas (2 at codon 248, 11 at codon 249, 1 at codon 372, 9 at codon 375, 2 at codon 652). Although no significant relation was found between the occurrence of TD mutations and patient age and clinical status, the incidence of TD mutations was significantly higher in low-grade or superficial tumors than high-grade or muscle invasive tumors.
These findings indicate that TD mutations in the FGFR3 gene do not cause disease progression of bladder carcinoma.
成纤维细胞生长因子受体3（FGFR3）的点突变与常染色体显性遗传的人类骨骼疾病相关，如致死性骨发育不全（TD）。然而，在一小部分膀胱癌中也报道了点突变，提示其致癌作用。鉴于这些发现，作者在一大系列膀胱癌中研究了FGFR3基因中TD突变的发生率，以阐明其在膀胱癌进展中的作用。
采用聚合酶链反应-限制性片段长度多态性、单链构象多态性及DNA测序，对81例膀胱移行细胞癌标本筛查TD中已报道的FGFR3突变（密码子248、249、372、373、375、652、809）。
81例癌中25例检测到点突变（密码子248处2例，密码子249处11例，密码子372处1例，密码子375处9例，密码子652处2例）。虽然未发现TD突变的发生与患者年龄及临床状况之间存在显著相关性，但低级别或表浅肿瘤中TD突变的发生率显著高于高级别或肌层浸润性肿瘤。
这些发现表明FGFR3基因中的TD突变不会导致膀胱癌的疾病进展。
