Molecular characterization of permanent cell lines from primary, metastatic and recurrent malignant peripheral nerve sheath tumors (MPNST) with underlying neurofibromatosis-1 Journal Article


Authors: Fang, Y.; Elahi, A.; Denley, R. C.; Rao, P. H.; Brennan, M. F.; Jhanwar, S. C.
Article Title: Molecular characterization of permanent cell lines from primary, metastatic and recurrent malignant peripheral nerve sheath tumors (MPNST) with underlying neurofibromatosis-1
Abstract: Malignant peripheral nerve sheath tumors (MPNSTs) develop in patients with underlying NF1, and usually arise as a result of malignant transformation of a pre-existing plexiform neurofibroma. The clonal cytogenetic abnormalities reported in primary MPNST include complex karyotypes with chromosome numbers in the triploid or tetraploid range with recurrent abnormalities of several chromosomes including losses or imbalances. As a prelude to cell biological, pharmacological, and functional studies to investigate pathways and gene(s) associated with multistep tumorigenesis, which includes progression, metastasis and resistance to therapy in MPNST, detailed molecular cytogenetic and genetic analyses of cell lines from primary, metastatic and recurrent MPNST with underlying NF1 disorder have been performed. The clonal cytogenetic abnormalities detected in the primary tumor cell line were similar to those observed in primary cultures of this tumor. Due to the complexity of the rearrangements seen by G- banded karyotype analysis, further characterization of the clonal abnormalities in these three cell lines was performed by molecular cytogenetic techniques, including CGH and SKY. CGH analysis detected recurrent deletions of 9p, 12q21-q32, complete losses of the X-chromosome, and gains of the chromosomal segment 17q25 in all three cell lines. SKY analysis detected extensive clonal abnormalities in these cell lines. The nature and the alterations of the cell cycle regulators, particularly those associated with Gl-S.
Keywords: adolescent; human cell; cell proliferation; in situ hybridization, fluorescence; neurofibromatosis; neurofibromatosis 1; metastasis; neoplasm recurrence, local; recurrence; tumor cells, cultured; immunoenzyme techniques; cell culture; rna, messenger; oligonucleotide array sequence analysis; fibroblasts; tumor suppressor protein p53; chromosome aberrations; loss of heterozygosity; chromosome deletion; cell cycle regulation; cell cycle regulators; malignant peripheral nerve sheath tumor; molecular characterization; mpnst; nm-23h1; chromosome analysis; chromosome loss; karyotype; nerve sheath tumor; peripheral nerve tumor; blotting, northern; chromosomes, human; comparative genomic hybridization; genes, neurofibromatosis 1; karyotyping; nerve sheath neoplasms
Journal Title: Anticancer Research
Volume: 29
Issue: 4
ISSN: 0250-7005
Publisher: International Institute of Anticancer Research  
Date Published: 2009-04-01
Start Page: 1255
End Page: 1262
Language: English
PUBMED: 19414372
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 30 November 2010" - "CODEN: ANTRD" - "Source: Scopus"