Gene 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.

Abstract	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.
Authors	Fausto J Rodriguez, Caterina Giannini, Yan W Asmann, Mukesh K Sharma, Arie Perry, Kathleen M Tibbetts, Robert B Jenkins, Bernd W Scheithauer, Shrikant Anant, Sarah Jenkins, Charles G Eberhart, Jann N Sarkaria, David H Gutmann
Journal	Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 67 Issue 12 Pg. 1194-204 (Dec 2008) ISSN: 0022-3069 [Print] England
PMID	19018242 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Biomarkers, Tumor Isoenzymes Nerve Tissue Proteins Aldehyde Dehydrogenase 1 Family Aldehyde Dehydrogenase ALDH1A1 protein, human ALDH1A1 protein, mouse Retinal Dehydrogenase Oxidoreductases Acting on CH-NH Group Donors formyltetrahydrofolate dehydrogenase
Topics	Adolescent Adult Aldehyde Dehydrogenase (genetics, metabolism) Aldehyde Dehydrogenase 1 Family Animals Astrocytoma (diagnosis, enzymology, genetics) Biomarkers, Tumor (genetics, metabolism) Brain Neoplasms (diagnosis, enzymology, genetics) Cell Transformation, Neoplastic (genetics, metabolism) Child Child, Preschool Female Gene Expression Profiling (methods) Gene Expression Regulation, Neoplastic (genetics) Humans Infant Isoenzymes (genetics, metabolism) Male Mice Middle Aged Neoplasm Invasiveness (genetics) Nerve Tissue Proteins (genetics, metabolism) Neurofibromatosis 1 (complications) Oxidoreductases Acting on CH-NH Group Donors Retinal Dehydrogenase Young Adult

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