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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1194-1204
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume67
Issue number12
DOIs
StatePublished - Dec 1 2008

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Astrocytoma
Gene Expression Profiling
Biomarkers
Neurofibromatosis 1
aldehyde dehydrogenase 1
Genes
Glioma
Young Adult
Neoplasms
Histology
Necrosis

Keywords

  • Brain tumor
  • Glioma
  • Microarray
  • Molecular signature
  • Neurofibromatosis
  • Pilocytic astrocytoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

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. / Rodriguez, Fausto J.; Giannini, Caterina; Asmann, Yan W.; Sharma, Mukesh K.; Perry, Arie; Tibbetts, Kathleen M.; Jenkins, Robert B.; Scheithauer, Bernd W.; Anant, Shrikant; Jenkins, Sarah; Eberhart, Charles G.; Sarkaria, Jann N.; Gutmann, David H.

In: Journal of Neuropathology and Experimental Neurology, Vol. 67, No. 12, 01.12.2008, p. 1194-1204.

Research output: Contribution to journalArticle

Rodriguez, Fausto J. ; Giannini, Caterina ; Asmann, Yan W. ; Sharma, Mukesh K. ; Perry, Arie ; Tibbetts, Kathleen M. ; Jenkins, Robert B. ; Scheithauer, Bernd W. ; Anant, Shrikant ; Jenkins, Sarah ; Eberhart, Charles G. ; Sarkaria, Jann N. ; Gutmann, David H. / 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. In: Journal of Neuropathology and Experimental Neurology. 2008 ; Vol. 67, No. 12. pp. 1194-1204.
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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.",
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AU - Rodriguez, Fausto J.

AU - Giannini, Caterina

AU - Asmann, Yan W.

AU - Sharma, Mukesh K.

AU - Perry, Arie

AU - Tibbetts, Kathleen M.

AU - Jenkins, Robert B.

AU - Scheithauer, Bernd W.

AU - Anant, Shrikant

AU - Jenkins, Sarah

AU - Eberhart, Charles G.

AU - Sarkaria, Jann N.

AU - Gutmann, David H.

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