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Genetics of progression of pleomorphic xanthoastrocytoma (PXA) in the pediatric population
Author(s) -
Hazrati LiliNaz,
Solomon Lauren,
Lee Eric,
Monsalves Eric,
Ma Jing,
Tabori Uri,
Hawkins Cynthia
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.172.1
Subject(s) - biology , malignancy , wnt signaling pathway , gene , population , pathology , cancer research , genetics , medicine , environmental health
Recent publications suggest that with time, PXAs, rare low grade astrocytomas of children and young adults, may acquire anaplastic features and progress to malignancy with a prognosis similar to high grade astrocytomas. As malignant progression of low grade astrocytomas is rare in children, we sought to uncover the genetic changes that underlie this transformation. A search of the databases at our institution (1985–2007) identified 7 patients with a primary diagnosis of PXA. Most had multiple recurrences, with two fatalities. Extracted DNA was hybridized onto 500K SNP mapping gene arrays (Affymetrix) and gene copy‐number changes identified (dCHIP). Analysis of copy‐number changes at first presentation showed few alterations, mainly corresponding to genes within the Wnt/Cadherin pathways. However, with recurrences, the number of genes with copy‐number changes increased and other pathways implicated in cell proliferation, motility and invasiveness became modified, with prominent involvement of the integrin, Ras, and EGFR pathways. These data show that recurring PXAs acquire cumulative and progressive genetic changes that contribute to their rapid growth and increasing invasiveness and thus their less favorable outcome. Further, our experience supports the idea that in the pediatric population, PXAs are prone to recurrences and do not behave as typical low grade astrocytomas. Funding: CIHR.