Confirmation of a double-hit model for the NF1 gene in benign neurofibromas

Eduard Serra, Susana Puig, David Otero, Antonia Gaona, Helena Kruyer, Elisabet Ars, Xavier P. Estivill, Conxi Lázaro

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

Neurofibroma is a benign tumor that arises from small or large nerves. This neoplastic lesion is a common feature of neurofibromatosis type 1 (NF1), one of the most common autosomal dominant disorders. The NF1 gene codes for a protein called 'neurofibromin.' It possesses a region that shares a high homology with the family of GTPase-activating proteins, which are negative regulators of RAS function and thereby control cell growth and differentiation. The evidence points to the NF1 gene being a tumor-suppressor gene. NF1 patients also have an increased incidence of certain malignant tumors that are believed to follow the 'two hit' hypothesis, with one allele constitutionally inactivated and the other somatically mutated. Recently, somatic loss of heterozygosity (LOH) has been described for neurofibromas, and mutations in both copies of the NF1 gene have been reported for a dermal neurofibroma. The aim of our study was the analysis of the NF1 locus in benign neurofibromas in NF1 patients. We performed LOH analysis on 60 neurofibromas belonging to 17 patients, 9 of them with family history of the disease and 8 of them sporadic. We have analyzed five intragenic NF1 markers and six extragenic markers, and we have found LOH in 25% of the neurofibromas (corresponding to 53% of the patients). In addition, we found that in the neurofibromas of patients from familial cases the deletions occurred in the allele that is not transmitted with the disease, indicating that both copies of the NF1 gene were inactivated in these tumors. Therefore, the recent reports mentioned above, together with our findings, strongly support the double inactivation of the NF1 gene in benign neurofibromas.

Original languageEnglish
Pages (from-to)512-519
Number of pages8
JournalAmerican Journal of Human Genetics
Volume61
Issue number3
Publication statusPublished - Sep 1997
Externally publishedYes

Fingerprint

Neurofibromatosis 1 Genes
Neurofibroma
Neurofibromatosis 1
Loss of Heterozygosity
Neurofibromin 1
Alleles
GTPase-Activating Proteins
Neoplasms
Tumor Suppressor Genes
Cell Differentiation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Serra, E., Puig, S., Otero, D., Gaona, A., Kruyer, H., Ars, E., ... Lázaro, C. (1997). Confirmation of a double-hit model for the NF1 gene in benign neurofibromas. American Journal of Human Genetics, 61(3), 512-519.

Confirmation of a double-hit model for the NF1 gene in benign neurofibromas. / Serra, Eduard; Puig, Susana; Otero, David; Gaona, Antonia; Kruyer, Helena; Ars, Elisabet; Estivill, Xavier P.; Lázaro, Conxi.

In: American Journal of Human Genetics, Vol. 61, No. 3, 09.1997, p. 512-519.

Research output: Contribution to journalArticle

Serra, E, Puig, S, Otero, D, Gaona, A, Kruyer, H, Ars, E, Estivill, XP & Lázaro, C 1997, 'Confirmation of a double-hit model for the NF1 gene in benign neurofibromas', American Journal of Human Genetics, vol. 61, no. 3, pp. 512-519.
Serra E, Puig S, Otero D, Gaona A, Kruyer H, Ars E et al. Confirmation of a double-hit model for the NF1 gene in benign neurofibromas. American Journal of Human Genetics. 1997 Sep;61(3):512-519.
Serra, Eduard ; Puig, Susana ; Otero, David ; Gaona, Antonia ; Kruyer, Helena ; Ars, Elisabet ; Estivill, Xavier P. ; Lázaro, Conxi. / Confirmation of a double-hit model for the NF1 gene in benign neurofibromas. In: American Journal of Human Genetics. 1997 ; Vol. 61, No. 3. pp. 512-519.
@article{fc87bf50e53f4167a550663ddf94546f,
title = "Confirmation of a double-hit model for the NF1 gene in benign neurofibromas",
abstract = "Neurofibroma is a benign tumor that arises from small or large nerves. This neoplastic lesion is a common feature of neurofibromatosis type 1 (NF1), one of the most common autosomal dominant disorders. The NF1 gene codes for a protein called 'neurofibromin.' It possesses a region that shares a high homology with the family of GTPase-activating proteins, which are negative regulators of RAS function and thereby control cell growth and differentiation. The evidence points to the NF1 gene being a tumor-suppressor gene. NF1 patients also have an increased incidence of certain malignant tumors that are believed to follow the 'two hit' hypothesis, with one allele constitutionally inactivated and the other somatically mutated. Recently, somatic loss of heterozygosity (LOH) has been described for neurofibromas, and mutations in both copies of the NF1 gene have been reported for a dermal neurofibroma. The aim of our study was the analysis of the NF1 locus in benign neurofibromas in NF1 patients. We performed LOH analysis on 60 neurofibromas belonging to 17 patients, 9 of them with family history of the disease and 8 of them sporadic. We have analyzed five intragenic NF1 markers and six extragenic markers, and we have found LOH in 25{\%} of the neurofibromas (corresponding to 53{\%} of the patients). In addition, we found that in the neurofibromas of patients from familial cases the deletions occurred in the allele that is not transmitted with the disease, indicating that both copies of the NF1 gene were inactivated in these tumors. Therefore, the recent reports mentioned above, together with our findings, strongly support the double inactivation of the NF1 gene in benign neurofibromas.",
author = "Eduard Serra and Susana Puig and David Otero and Antonia Gaona and Helena Kruyer and Elisabet Ars and Estivill, {Xavier P.} and Conxi L{\'a}zaro",
year = "1997",
month = "9",
language = "English",
volume = "61",
pages = "512--519",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Confirmation of a double-hit model for the NF1 gene in benign neurofibromas

AU - Serra, Eduard

AU - Puig, Susana

AU - Otero, David

AU - Gaona, Antonia

AU - Kruyer, Helena

AU - Ars, Elisabet

AU - Estivill, Xavier P.

AU - Lázaro, Conxi

PY - 1997/9

Y1 - 1997/9

N2 - Neurofibroma is a benign tumor that arises from small or large nerves. This neoplastic lesion is a common feature of neurofibromatosis type 1 (NF1), one of the most common autosomal dominant disorders. The NF1 gene codes for a protein called 'neurofibromin.' It possesses a region that shares a high homology with the family of GTPase-activating proteins, which are negative regulators of RAS function and thereby control cell growth and differentiation. The evidence points to the NF1 gene being a tumor-suppressor gene. NF1 patients also have an increased incidence of certain malignant tumors that are believed to follow the 'two hit' hypothesis, with one allele constitutionally inactivated and the other somatically mutated. Recently, somatic loss of heterozygosity (LOH) has been described for neurofibromas, and mutations in both copies of the NF1 gene have been reported for a dermal neurofibroma. The aim of our study was the analysis of the NF1 locus in benign neurofibromas in NF1 patients. We performed LOH analysis on 60 neurofibromas belonging to 17 patients, 9 of them with family history of the disease and 8 of them sporadic. We have analyzed five intragenic NF1 markers and six extragenic markers, and we have found LOH in 25% of the neurofibromas (corresponding to 53% of the patients). In addition, we found that in the neurofibromas of patients from familial cases the deletions occurred in the allele that is not transmitted with the disease, indicating that both copies of the NF1 gene were inactivated in these tumors. Therefore, the recent reports mentioned above, together with our findings, strongly support the double inactivation of the NF1 gene in benign neurofibromas.

AB - Neurofibroma is a benign tumor that arises from small or large nerves. This neoplastic lesion is a common feature of neurofibromatosis type 1 (NF1), one of the most common autosomal dominant disorders. The NF1 gene codes for a protein called 'neurofibromin.' It possesses a region that shares a high homology with the family of GTPase-activating proteins, which are negative regulators of RAS function and thereby control cell growth and differentiation. The evidence points to the NF1 gene being a tumor-suppressor gene. NF1 patients also have an increased incidence of certain malignant tumors that are believed to follow the 'two hit' hypothesis, with one allele constitutionally inactivated and the other somatically mutated. Recently, somatic loss of heterozygosity (LOH) has been described for neurofibromas, and mutations in both copies of the NF1 gene have been reported for a dermal neurofibroma. The aim of our study was the analysis of the NF1 locus in benign neurofibromas in NF1 patients. We performed LOH analysis on 60 neurofibromas belonging to 17 patients, 9 of them with family history of the disease and 8 of them sporadic. We have analyzed five intragenic NF1 markers and six extragenic markers, and we have found LOH in 25% of the neurofibromas (corresponding to 53% of the patients). In addition, we found that in the neurofibromas of patients from familial cases the deletions occurred in the allele that is not transmitted with the disease, indicating that both copies of the NF1 gene were inactivated in these tumors. Therefore, the recent reports mentioned above, together with our findings, strongly support the double inactivation of the NF1 gene in benign neurofibromas.

UR - http://www.scopus.com/inward/record.url?scp=0030850675&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030850675&partnerID=8YFLogxK

M3 - Article

VL - 61

SP - 512

EP - 519

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 3

ER -