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Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association

(2009) CANCER RESEARCH. 69(18). p.7393-7401
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Abstract
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 thermo regulatory shunt concentrated in the fingers and toes. We report 11 individuals with NF1 who harbored 20 glomus tumors of the fingers and 1 in the toe; 5 individuals had multiple glomus tumors. We hypothesized that biallelic inactivation of NF1 underlies the pathogenesis of these tumors. In 12 NF1-associated glomus tumors, we used cell culture and laser capture microdissection to isolate DNA. We also analyzed two sporadic (not NF1-associated) glomus tumors. Genetic analysis showed germ line and somatic NF1 mutations in seven tumors. RAS mitogen-activated protein kinase hyperactivation was observed in cultured NF1(-/-) glomus cells, reflecting a lack of inhibition of the pathway by functional neurofibromin, the protein product of NFI. No abnormalities in NF1 or RAS mitogen-activated protein kinase 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.
Keywords
SUPPRESSOR, MODEL, POLYMORPHISM, PATHOGENESIS, REPEAT, MUTATIONS, IDENTIFICATION, HEREDITARY CANCER, NF1 GENE, METHYLATION-SPECIFIC PCR

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Chicago
Brems, Hilde, Caroline Park, Ophélia Maertens, Alexander Pemov, Ludwine Messia, Meena Upadhyaya, Kathleen Claes, et al. 2009. “Glomus Tumors in Neurofibromatosis Type 1: Genetic, Functional, and Clinical Evidence of a Novel Association.” Cancer Research 69 (18): 7393–7401.
APA
Brems, Hilde, Park, C., Maertens, O., Pemov, A., Messia, L., Upadhyaya, M., Claes, K., et al. (2009). Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association. CANCER RESEARCH, 69(18), 7393–7401.
Vancouver
1.
Brems H, Park C, Maertens O, Pemov A, Messia L, Upadhyaya M, et al. Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association. CANCER RESEARCH. 2009;69(18):7393–401.
MLA
Brems, Hilde, Caroline Park, Ophélia Maertens, et al. “Glomus Tumors in Neurofibromatosis Type 1: Genetic, Functional, and Clinical Evidence of a Novel Association.” CANCER RESEARCH 69.18 (2009): 7393–7401. Print.
@article{1844273,
  abstract     = {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 thermo regulatory shunt concentrated in the fingers and toes. We report 11 individuals with NF1 who harbored 20 glomus tumors of the fingers and 1 in the toe; 5 individuals had multiple glomus tumors. We hypothesized that biallelic inactivation of NF1 underlies the pathogenesis of these tumors. In 12 NF1-associated glomus tumors, we used cell culture and laser capture microdissection to isolate DNA. We also analyzed two sporadic (not NF1-associated) glomus tumors. Genetic analysis showed germ line and somatic NF1 mutations in seven tumors. RAS mitogen-activated protein kinase hyperactivation was observed in cultured NF1(-/-) glomus cells, reflecting a lack of inhibition of the pathway by functional neurofibromin, the protein product of NFI. No abnormalities in NF1 or RAS mitogen-activated protein kinase 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.},
  author       = {Brems, Hilde and Park, Caroline and Maertens, Oph{\'e}lia and Pemov, Alexander and Messia, Ludwine and Upadhyaya, Meena and Claes, Kathleen and Beert, Eline and Peeters, Kristel and Mautner, Victor and Sloan, Jennifer L and Yao, Lawrence and Lee, Chyi-Chia Richard and Sciot, Raf and De Smet, Luc and Legius, Eric and Stewart, Douglas R},
  issn         = {0008-5472},
  journal      = {CANCER RESEARCH},
  keyword      = {SUPPRESSOR,MODEL,POLYMORPHISM,PATHOGENESIS,REPEAT,MUTATIONS,IDENTIFICATION,HEREDITARY CANCER,NF1 GENE,METHYLATION-SPECIFIC PCR},
  language     = {eng},
  number       = {18},
  pages        = {7393--7401},
  title        = {Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association},
  url          = {http://dx.doi.org/10.1158/0008-5472.CAN-09-1752},
  volume       = {69},
  year         = {2009},
}

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