Cancer-related gene expression profiles in NF1-associated pilocytic astrocytomas

被引:41
作者
Li, J
Perry, A
James, CD
Gutmann, DH
机构
[1] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Neuropathol, St Louis, MO 63110 USA
[3] Mayo Clin & Mayo Fdn, Div Expt Pathol, Rochester, MN 55905 USA
关键词
D O I
10.1212/WNL.56.7.885
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: individuals affected with neurofibromatosis 1 (NF1) develop juvenile pilocytic astrocytomas (JPA) at an increased frequency, suggesting that the NF1 gene product, neurofibromin, functions as a negative growth regulator for astrocytes. Previously, the authors demonstrated that NF1-associated astrocytomas exhibit deletions and loss of NF1 gene expression on the DNA and protein levels. However, Little is known about additional genetic events in clinically and radiographically progressive NF1-associated pilocytic astrocytomas. Objective/methods: To understand the potential role of cooperating genetic events in the development of these low-grade tumors, the authors used immunohistochemistry and selected confirmatory Western blots to examine nine symptomatic NF1-associated pilocytic astrocytomas for gene products whose expression patterns are altered in fibrillary astrocytomas. Results: The authors demonstrate that p53, p16, retinoblastoma (RB), epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), platelet-derived growth factor A (PDGF-A) and PDGF receptor alpha (PDGF-R alpha) protein expression profiles are not altered in NF1-associated pilocytic astrocytomas. Similar to their sporadic counterparts, NF1-associated JPA also strongly expressed PENS, a marker of post-O2A stage oligodendroglial precursor cells. Conclusions: These results suggest that NF1-associated pilocytic astrocytomas lack the genetic changes typically associated with the more clinically aggressive fibrillary astrocytomas and lay the foundation for future studies to identify NF1 JPA-specific alterations.
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页码:885 / 890
页数:6
相关论文
共 28 条
[1]   THE NF1 LOCUS ENCODES A PROTEIN FUNCTIONALLY RELATED TO MAMMALIAN GAP AND YEAST IRA PROTEINS [J].
BALLESTER, R ;
MARCHUK, D ;
BOGUSKI, M ;
SAULINO, A ;
LETCHER, R ;
WIGLER, M ;
COLLINS, F .
CELL, 1990, 63 (04) :851-859
[2]  
BOLLAG G, 1991, ANNU REV CELL BIOL, V7, P601, DOI 10.1146/annurev.cellbio.7.1.601
[3]  
BRUCH LA, IN PRESS HUMAN PATHO
[4]  
BURGER PC, 2000, WHO CLASSIFICATION T, P45
[5]   Signal transduction pathways and their relevance in human astrocytomas [J].
Feldkamp, MM ;
Lau, N ;
Guha, A .
JOURNAL OF NEURO-ONCOLOGY, 1997, 35 (03) :223-248
[6]   The PEN5 epitope identifies an oligodendrocyte precursor cell population and pilocytic astrocytomas [J].
Figarella-Branger, D ;
Daniel, L ;
André, P ;
Guia, S ;
Renaud, W ;
Monti, G ;
Vivier, E ;
Rougon, G .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (04) :1261-1269
[7]  
Friedman JM, 1999, Neurofibromatosis : phenotype, natural history, and pathogenesis
[8]   EXPRESSION OF PDGF AND PDGF RECEPTORS IN HUMAN ASTROCYTOMA OPERATION SPECIMENS SUPPORTS THE EXISTENCE OF AN AUTOCRINE LOOP [J].
GUHA, A ;
DASHNER, K ;
BLACK, PM ;
WAGNER, JA ;
STILES, CD .
INTERNATIONAL JOURNAL OF CANCER, 1995, 60 (02) :168-173
[9]   Loss of neurofibromatosis 1 (NF1) gene expression in NF1-associated pilocytic astrocytomas [J].
Gutmann, DH ;
Donahoe, J ;
Brown, T ;
James, CD ;
Perry, A .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2000, 26 (04) :361-367
[10]   PRECOCIOUS PUBERTY IN CHILDREN WITH NEUROFIBROMATOSIS TYPE-1 [J].
HABIBY, R ;
SILVERMAN, B ;
LISTERNICK, R ;
CHARROW, J .
JOURNAL OF PEDIATRICS, 1995, 126 (03) :364-367