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RECURRENT COPY NUMBER ALTERATIONS IN LOW-GRADE AND ANAPLASTIC PLEOMORPHIC XANTHOASTROCYTOMA WITH AND WITHOUT BRAF V600E MUTATION
- Publication Year :
- 2017
-
Abstract
- Pleomorphic xanthoastrocytoma (PXA) is a rare localized glioma characterized by frequent BRAF V600E mutation and CDKN2A/B deletion. We explored the association of copy-number variants (CNVs) with BRAF mutations, tumor grade, and patient survival in a cohort of 41 PXA patients using OncoScan chromosomal microarray. Primary resection specimens were available in 38 cases, including 24 PXA and 14 anaplastic PXA (A-PXA), 23 BRAF V600E mutant tumors (61%). CNVs were identified in all cases and most frequently involved chromosome 9 with homozygous CDKN2A/B deletion (n = 33, 87%), a higher proportion than previously detected by comparative genomic hybridization (50%–60%) (37). CDKN2A/B deletion was present in similar proportion of PXA (83%), A-PXA (93%), BRAF V600E (87%), and wild-type (87%) tumors. Whole chromosome gains/losses were frequent, including gains +7 (n = 15), +2 (n = 11), +5 (n = 10), +21 (n = 10), +20 (n = 9), +12 (n = 8), +15 (n = 8), and losses −22 (n = 11), −14 (n = 7), −13 (n = 5). Losses and copy-neutral loss of heterozygosity were significantly more common in A-PXA, involving chromosomes 22 (P = 0.009) and 14 (P = 0.03). Amplification of 8p and 12q was identified in a single tumor. Histologic grade was a robust predictor of overall survival (P = 0.003), while other copy-number changes, including CDKN2A/B deletion, did not show significant association with survival. Distinct histologic patterns of anaplasia included increased mitotic activity in an otherwise classic PXA or associated with small cell, fibrillary, or epithelioid morphology, with loss of SMARCB1 expression in one case. In 10 cases, matched specimens were compared, including A-PXA with areas of distinct low- and high-grade morphology (n = 2), matched primary/tumor recurrence (n = 7), or both (n = 1). Copy-number changes on recurrence/anaplastic transformation were complex and highly variable, from nearly identical profiles to numerous copy-number changes. Overall, we confirm CDKN2A/B deletion as key a feature of PXA not associated with tumor grade or BRAF mutation, but central to the underlying genetics of PXA.
- Subjects :
- Adult
Male
Proto-Oncogene Proteins B-raf
Adolescent
DNA Copy Number Variations
Supratentorial Neoplasm
Chromosome Aberration
Article
BRAF
Follow-Up Studie
Young Adult
Cyclin-Dependent Kinase Inhibitor p18
Humans
Cerebellar Neoplasms
Child
anaplastic pleomorphic xanthoastrocytoma
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p15
Chromosome Aberrations
low-grade glioma
Cerebellar Neoplasm
Supratentorial Neoplasms
Glioma
SMARCB1 Protein
Middle Aged
Child, Preschool
Mutation
pleomorphic xanthoastrocytoma
Female
Neoplasm Recurrence, Local
Human
Follow-Up Studies
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.pmid.dedup....58f8b9916e06e11899b3562e6225fecc