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Molecular heterogeneity in malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1
- Source :
- Human Genomics, Vol 6, Iss 1, p 18 (2012), Human Genomics
- Publication Year :
- 2012
- Publisher :
- BMC, 2012.
-
Abstract
- Neurofibromatosis type-1 (NF1), resulting from NF1 gene loss of function, is characterized by an increased risk of developing benign and malignant peripheral nerve sheath tumors (MPNSTs). Whereas the cellular heterogeneity of NF1-associated tumors has been well studied, the molecular heterogeneity of MPNSTs is still poorly understood. Mutational heterogeneity within these malignant tumors greatly complicates the study of the underlying mechanisms of tumorigenesis. We have explored this molecular heterogeneity by performing loss of heterozygosity (LOH) analysis of the NF1, TP53, RB1, PTEN, and CDKN2A genes on sections of 10 MPNSTs derived from 10 unrelated NF1 patients. LOH data for the TP53 gene was found to correlate with the results of p53 immunohistochemical analysis in the same tumor sections. Further, approximately 70% of MPNSTs were found to display intra-tumoral molecular heterogeneity as evidenced by differences in the level of LOH between different sections of the same tumor samples. This study constitutes the first systematic analysis of molecular heterogeneity within MPNSTs derived from NF1 patients. Appreciation of the existence of molecular heterogeneity in NF1-associated tumors is important not only for optimizing somatic mutation detection, but also for understanding the mechanisms of NF1 tumorigenesis, a prerequisite for the development of specifically targeted cancer therapeutics.
- Subjects :
- Genetic Markers
congenital, hereditary, and neonatal diseases and abnormalities
Neurofibromatosis 1
lcsh:QH426-470
Loss of Heterozygosity
lcsh:Medicine
medicine.disease_cause
Retinoblastoma Protein
Nerve Sheath Neoplasms
Loss of heterozygosity
Germline mutation
Risk Factors
CDKN2A
Genes, Neurofibromatosis 1
Drug Discovery
Genetics
medicine
Malignant peripheral nerve sheath tumors
Humans
PTEN
TP53
Neurofibromatosis
Molecular Biology
neoplasms
biology
Genes, p16
lcsh:R
PTEN Phosphohydrolase
Cancer
Genes, p53
medicine.disease
eye diseases
Molecular heterogeneity
nervous system diseases
lcsh:Genetics
Genetic Loci
Mutation
biology.protein
Cancer research
Molecular Medicine
Tumor Suppressor Protein p53
Primary Research
Carcinogenesis
Nerve sheath neoplasm
Neurofibromatosis type 1
Subjects
Details
- Language :
- English
- ISSN :
- 14797364
- Volume :
- 6
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Human Genomics
- Accession number :
- edsair.doi.dedup.....31ad0411c34bb49b090f733ff6ffeb9d