Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association.
Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association.
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DOI：
10.1158/0008-5472.can-09-1752
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发表时间：
2009-09-15
期刊：
影响因子：
11.2
通讯作者：
Stewart DR
中科院分区：
文献类型：
--
作者：
Brems H;Park C;Maertens O;Pemov A;Messiaen L;Upadhyaya M;Claes K;Beert E;Peeters K;Mautner V;Sloan JL;Yao L;Lee CC;Sciot R;De Smet L;Legius E;Stewart DR
Neurofibromatosis type 1 (NF1) is a common disorder that arises secondary to mutations in the tumor suppressor gene NF1. Glomus tumors are small, benign but painful tumors that originate from the glomus body, a thermoregulatory shunt concentrated in the fingers and toes. We report eleven individuals with NF1 who harbored 20 glomus tumors of the fingers and one in the toe; five individuals had multiple glomus tumors. We hypothesized that bi-allelic inactivation of NF1 underlies the pathogenesis of these tumors. In twelve NF1-associated glomus tumors, we used cell culture and laser capture micro-dissection to isolate DNA. We also analyzed two sporadic (not-NF1-associated) glomus tumors. Genetic analysis showed germline and somatic NF1 mutations in seven tumors. RAS-MAPK hyper-activation was observed in cultured NF1-/- glomus cells, reflecting a lack of inhibition of the pathway by functional neurofibromin, the protein product of NF1. No abnormalities in NF1 or RAS-MAPK activation were found in sporadic glomus tumors. By comparative genomic hybridization, we observed amplification of the 3′-end of CRTAC1 and a deletion of the 5′-end of WASF1 in two NF1-associated glomus tumors. For the first time, we show that loss of neurofibromin function is crucial in the pathogenesis of glomus tumors in NF1. Glomus tumors of the fingers or toes should be considered as part of the tumor spectrum of NF1.
