Pilomyxoid Astrocytoma (PMA) Shows Significant Differences in Gene Expression vs. Pilocytic Astrocytoma (PA) and Variable Tendency Toward Maturation to PA

Abstract

Pilomyxoid astrocytomas (PMAs) manifest a more aggressive clinical course than pilocytic astrocytomas (PAs). Development of effective therapies demands a better biological understanding of PMA. We first conducted gene expression microarray analysis of 9 PMA and 13 PA from infra- and supra-tentorial sites. Unsupervised hierarchical clustering analysis demonstrated that tumors grouped according to anatomic site, not diagnosis. Gene expression profiles were then contrasted between 8 PMAs and 6 PAs, all supratentorial/hypothalamic/chiasmal. Clinical outcome of PMAs varied, with 4/4 patients with diencephalic syndrome succumbing to disease, one of whom showed bulky metastatic leptomeningeal spread at autopsy, with bimodal maturation to PA in some areas and de-differentiation to glioblastoma in others. A surviving child has undergone multiple surgical debulkings, with progressive maturation to PA over time. Ontology-enrichment analysis identified overexpression in PMAs of extracellular matrix and mitosis-related genes. Genes overexpressed in PMA versus PA, ranked according to fold-change, included developmental genes H19, DACT2, extracellular matrix collagens (COL2A1;COL1A1) and IGF2BP3 (IMP3), the latter previously identified as an adverse prognostic factor in PMA and PA.

The Emerging Roles of RNA Modifications in Glioblastoma

“…IGF2BP3 mRNA and protein levels are also upregulated in GBMs but not in lower grade astrocytomas [97]. Particularly, IGF2BP3 is one of the genes overexpressed in pilomyxoid astrocytomas (PMAs) compared with a less aggressive pilocytic astrocytomas (PAs), according to a gene expression microarray analysis of 9 PMAs and 13 PAs from infra-and supratentorial sites [98]. A microarray analysis in glioma cells shows that IGF2BP3 mediates regulation of direct targets at transcriptome associated with cell cycle process, whereas direct targets at the translatome participating in apoptosis related pathways [99].…”

Pilocytic astrocytoma with gangliocytic differentiation to pilomyxoid astrocytoma-expanding the morphological spectrum: Case report and literature review

“…Interestingly, a curious phenomenon of “maturation” has been described in a small subset of PMA with recurrent tumors “maturing” into PA-like neoplasms. [ 4 5 6 ] This is more frequently observed in tumors with “intermediate” features between PMA and PA designated as “intermediate pilomyxoid forms”. [ 3 6 ] The novelty in the present case is the presence of dysmorphic ganglion cells in PA in the 1 st resection with recurrent lesions depicting PMA-like features, an observation which is reverse of “maturation”.…”

“…However, the recent updated WHO classification has questioned assigning it a higher grade in view of considerable variation in their outcome in different studies. [ 3 ] An interesting and rare phenomenon of “maturation” has been observed with examples of PMA undergoing “maturation” to PA in subsequent recurrences[ 4 5 6 ] which is more commonly observed in the “intermediate” lesions. “Intermediate” lesions are tumor displaying features of typical PMA admixed with areas resembling classic PA.[ 4 ] Herein, we describe a rare example of PA with gangliocytic component showing a rapid regrowth within 1½ years with differentiation to PMA on the third recurrence.…”

Cytopathological features of pilomyxoid astrocytoma: a case report

“…However, PMAs affect infants whose body is still developing, and then PMA cells may also proliferate and develop in such an infantile microenvironment, in addition to tumour genetic alterations. Recently, KleinschmidtDeMasters et al 12 reported interesting information describing the molecular analysis of PMAs, including the difference in developmental gene alterations among PMA, PA and PMA cases showing the tendency towards maturation to PA. For a better understanding of the maturation from PMA to PA, further clinicopathological and genetic analyses using a large number of PMA cases are needed.…”