Extensive mutation scanning of RET in sporadic medullary thyroid carcinoma and of RET and VHL in sporadic pheochromocytoma reveals involvement of these genes in only a minority of cases

被引:66
作者
Hofstra, RMW
Stelwagen, T
Stulp, RP
DeJong, D
Hulsbeek, M
Kamsteeg, EJ
VanDenBerg, A
Landsvater, RM
Vermey, A
Molenaar, WM
Lips, CJM
Buys, CHCM
机构
[1] UNIV GRONINGEN, DEPT MED GENET, NL-9713 AW GRONINGEN, NETHERLANDS
[2] UNIV GRONINGEN HOSP, DEPT SURG, DIV SURG ONCOL, GRONINGEN, NETHERLANDS
[3] UNIV GRONINGEN HOSP, DEPT PATHOL, GRONINGEN, NETHERLANDS
[4] UNIV UTRECHT HOSP, DEPT INTERNAL MED, UTRECHT, NETHERLANDS
关键词
D O I
10.1210/jc.81.8.2881
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Sporadic medullary thyroid carcinoma (MTC) and pheochromocytoma (PC) have been reported to be associated with some specific RET gene mutations. To assess the role of RET in the development of MTC and PC, we screened 14 sporadic MTC, two MTC-derived cell lines, and 5 sporadic PC cases for RET mutations by a systematic analysis of the whole coding sequence, including all intron-exon junctions. In only 6 of the 14 sporadic MTC we were able to detect a RET mutation. Apart from the Met(918)-->Thr mutation in 5 of the MTC cases, we found a 3-bp deletion in exon 11, only present in the tumor, in another case. Analysis of 2 cell lines revealed the Met(918)-->Thr mutation in 1 and a Cys(634)-->Trp mutation in the other cell line. A possible somatic nature of these mutations could not be confirmed because in neither case was constitutive DNA available. We conclude that a large pro portion of sporadic MTC must be due to mutations in an unidentified gene(s) other than RET. In none of the sporadic PC cases was a RET mutation found. As PC is a frequent complication in families suffering from von Hippel Lindau disease, for which mutations of the VHL gene are responsible, we also screened the 5 sporadic PC cases for VHL mutations. This revealed a Gly(164)-->Ser mutation in a single specimen. Thus, in PC, a large majority of tumors are due to mutations in an unidentified gene(s) other than RET and VHL.
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页码:2881 / 2884
页数:4
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