Ghent University Academic Bibliography

Advanced

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

Hilde Brems, Caroline Park, Ophélia Maertens, Alexander Pemov, Ludwine Messia, Meena Upadhyaya, Kathleen Claes UGent, Eline Beert, Kristel Peeters, Victor Mautner, et al. (2009) CANCER RESEARCH. 69(18). p.7393-7401
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
SUPPRESSOR, MODEL, POLYMORPHISM, PATHOGENESIS, REPEAT, MUTATIONS, IDENTIFICATION, HEREDITARY CANCER, NF1 GENE, METHYLATION-SPECIFIC PCR
journal title
CANCER RESEARCH
Cancer Res.
volume
69
issue
18
pages
7393 - 7401
Web of Science type
Article
Web of Science id
000269954000034
JCR category
ONCOLOGY
JCR impact factor
7.543 (2009)
JCR rank
13/163 (2009)
JCR quartile
1 (2009)
ISSN
0008-5472
DOI
10.1158/0008-5472.CAN-09-1752
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1844273
handle
http://hdl.handle.net/1854/LU-1844273
date created
2011-06-28 16:04:57
date last changed
2016-12-19 15:41:56
@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},
}

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.