Neurofibromas in NF1: Schwann cell origin and role of tumor environment.
Neurofibromatosis type 1 (NF1) is one of the most prevalent dominantly inherited genetic diseases of the nervous system. NF1 encodes a tumor suppressor whose functional loss results in the development of benign neurofibromas that can progress to malignancy. Neurofibromas are complex tumors composed of axonal processes, Schwann cells, fibroblasts, perineurial cells, and mast cells. Through use of a conditional (cre/lox) allele, we show that loss of NF1 in the Schwann cell lineage is sufficient to generate tumors. In addition, complete NF1-mediated tumorigenicity requires both a loss of NF1 in cells destined to become neoplastic as well as heterozygosity in non-neoplastic cells. The requirement for a permissive haploinsufficient environment to allow tumorigenesis may have therapeutic implications for NF1 and other familial cancers.
Zhu
Yuan
Y
Center for Developmental Biology, Department of Pathology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9133, USA.
Ghosh
Pritam
P
Charnay
Patrick
P
Burns
Dennis K
DK
Parada
Luis F
LF
D000483:Alleles; D000818:Animals; D001369:Axons / Q000648:ultrastructure; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003391:Cranial Nerves / Q000473:pathology; D046508:Culture Techniques; D005260:Female; D016514:Genes, Neurofibromatosis 1; D005838:Genotype; D006579:Heterozygote; D006965:Hyperplasia; D019656:Loss of Heterozygosity; D008297:Male; D008407:Mast Cells / Q000737:chemistry / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009455:Neurofibroma / Q000235:genetics / Q000473:pathology*; D009456:Neurofibromatosis 1 / Q000235:genetics / Q000473:pathology*; D010525:Peripheral Nerves / Q000473:pathology; D012583:Schwann Cells / Q000737:chemistry / Q000473:pathology*; D013127:Spinal Nerves / Q000473:pathology