Open AccessGene Expression Profiling of NF-1-Associated and Sporadic Pilocytic Astrocytoma Identifies Aldehyde Dehydrogenase 1 Family Member L1 (ALDH1L1) as an Underexpressed Candidate Biomarker in Aggressive Subtypes
Author(s) -
Fausto J. Rodríguez,
Caterina Giannini,
Yan W. Asmann,
Mukesh Kumar Sharma,
Arie Perry,
Kathleen M. Tibbetts,
Robert B. Jenkins,
Bernd W. Scheithauer,
Shrikant Anant,
Sarah M. Jenkins,
Charles G. Eberhart,
Jann N. Sarkaria,
David H. Gutmann
Publication year - 2008
Publication title -
journal of neuropathology and experimental neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.441
H-Index - 164
eISSN - 1554-6578
pISSN - 0022-3069
DOI - 10.1097/nen.0b013e31818fbe1e
Subject(s) - pilocytic astrocytoma , neurofibromatosis , gene expression profiling , biology , gene , microarray analysis techniques , pathology , cancer research , gene expression , glioma , microarray , astrocytoma , microbiology and biotechnology , medicine , genetics
Pilocytic astrocytomas (PAs) are World Health Organization Grade I gliomas; they most often affect children and young adults and occur in patients with neurofibromatosis type 1 (NF1). To identify genes that are differentially expressed in sporadic (S-PA) versus NF1-associated PAs (NF1-PAs) and those that might reflect differences in clinical behavior, we performed gene expression profiling using Affymetrix U133 Plus2.0 GeneChip arrays in 36 S-PAs and 11 NF1-PAs. Thirteen genes were overexpressed, and another 13 genes were underexpressed in NF1-PAs relative to S-PAs. Immunohistochemical studies performed on 103 tumors, representing 2 independently generated tissue microarrays, confirmed the differential expression of CUGBP2 (p = 0.0014), RANBP9 (p = 0.0075), ITGAV1 (p = 0.0001), and INFGR1 (p = 0.024) proteins. One of the underexpressed genes, aldehyde dehydrogenase 1 family member L1 (ALDH1L1), was also reduced in clinically aggressive compared with typical PAs (p = 0.01) and in PAs with increased cellularity and necrosis. Furthermore, in an additional independent set of tumors, weak to absent ALDH1L1 expression was found in 13 (72%) of 18 clinically aggressive PAs, in 8 (89%) of 9 PAs with pilomyxoid features, in 7 (70%) of 10 PAs with anaplastic transformation, and in 16 (76%) of 21 diffusely infiltrating astrocytomas of various grades. In summary, we have identified a molecular signature that distinguishes NF1-PA from S-PA and found that ALDH1L1 underexpression is associated with aggressive histology and/or biologic behavior.