Glomus Tumors in Neurofibromatosis Type 1: Genetic, Functional, and Clinical Evidence of a Novel Association
| العنوان: | Glomus Tumors in Neurofibromatosis Type 1: Genetic, Functional, and Clinical Evidence of a Novel Association |
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| المؤلفون: | Hilde, Brems, Caroline, Park, Ophélia, Maertens, Alexander, Pemov, Ludwine, Messiaen, Ludwine, Messia, Meena, Upadhyaya, Kathleen, Claes, Eline, Beert, Kristel, Peeters, Victor, Mautner, Jennifer L, Sloan, Lawrence, Yao, Chyi-Chia Richard, Lee, Raf, Sciot, Luc, De Smet, Eric, Legius, Douglas R, Stewart |
| المصدر: | Cancer Research. 69:7393-7401 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, Cancer Research, Pathology, medicine.medical_specialty, Neurofibromatosis 1, Adolescent, Tumor suppressor gene, MAP Kinase Signaling System, Gene Dosage, Polymerase Chain Reaction, Article, Germline, Young Adult, Glomus cell, Glomus body, Genes, Neurofibromatosis 1, Tumor Cells, Cultured, medicine, Humans, Gene Silencing, Neurofibromatosis, Child, neoplasms, Skin, Laser capture microdissection, Comparative Genomic Hybridization, biology, fungi, Fibroblasts, Middle Aged, Glomus Tumor, medicine.disease, Neurofibromin 1, Actins, eye diseases, nervous system diseases, Glomus tumor, Oncology, Receptors, Androgen, ras Proteins, biology.protein, Female |
| الوصف: | 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 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 NF1. 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. [Cancer Res 2009;69(18):7393–401] |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d08e592202c502b402ef75418b489c62Test https://doi.org/10.1158/0008-5472.can-09-1752Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d08e592202c502b402ef75418b489c62 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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