title: Whole Chromosome 7 Gain Predicts Higher Risk of Recurrence in Pediatric Pilocytic Astrocytomas Independently From KIAA1549-BRAF Fusion Status.
abstract: The most frequent genetic alteration identified in pediatric pilocytic astrocytomas and pilomyxoid variant is the KIAA1549-BRAF fusion, which typically results from a 2.0 Mb tandem duplication in chromosome band 7q34. Less frequent abnormalities include fusion genes,BRAF, FGFR, KRAS, and NF1 point mutations, and whole chromosome gains. To correlate genetic alterations with clinical course data, we retrospectively analyzed the tumors with pilocytic and pilomyxoid histology of a cohort of 116 pediatric patients, aged 5 months to 23 years. Gross total resection was associated with a decreased risk of recurrence (p = 0.001), supporting previous findings that complete tumor excision correlates with long-term and disease-free survival. We found no significant association between recurrence rate and the presence of the KIAA1549-BRAF fusion or BRAF mutation (p = 0.167). Interestingly, gain of whole chromosome 7 (WC7) was associated with a 4.7-fold increased risk of tumor recurrence, even after adjusting for surgical status (p = 0.025), and other genetic alterations. Using fluorescence in situ hybridization, we demonstrated that when WC7 gain accompanies the KIAA1549-BRAF fusion, the fusion likely arises first. This study highlights the utility of genetic studies for risk assessment of pilocytic and pilomyxoid astrocytomas, which may impact treatment selections.
authors.affiliation: From the Department of Pediatrics (JJR, AJW), Department of Pathology and Laboratory Medicine (MS), and Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (AJW); Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (JJR); Department of Bio- statistics and Epidemiology, Perelman School of Medicine at the Univer- sity of Pennsylvania, Philadelphia, Pennsylvania (LY); Department of Neurosurgery, Temple University School of Medicine, Philadelphia, Pennsylvania (TMF); Department of Pathology and Laboratory Medicine, Children s Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California (JAB).
authors.forename: Jacquelyn J
authors.initials: JJ
authors.lastname: Roth
authors.affiliation: From the Department of Pediatrics (JJR, AJW), Department of Pathology and Laboratory Medicine (MS), and Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (AJW); Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (JJR); Department of Bio- statistics and Epidemiology, Perelman School of Medicine at the Univer- sity of Pennsylvania, Philadelphia, Pennsylvania (LY); Department of Neurosurgery, Temple University School of Medicine, Philadelphia, Pennsylvania (TMF); Department of Pathology and Laboratory Medicine, Children s Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California (JAB).
authors.forename: Tamara M
authors.initials: TM
authors.lastname: Fierst
authors.affiliation: From the Department of Pediatrics (JJR, AJW), Department of Pathology and Laboratory Medicine (MS), and Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (AJW); Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (JJR); Department of Bio- statistics and Epidemiology, Perelman School of Medicine at the Univer- sity of Pennsylvania, Philadelphia, Pennsylvania (LY); Department of Neurosurgery, Temple University School of Medicine, Philadelphia, Pennsylvania (TMF); Department of Pathology and Laboratory Medicine, Children s Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California (JAB).
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Waanders
authors.affiliation: From the Department of Pediatrics (JJR, AJW), Department of Pathology and Laboratory Medicine (MS), and Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (AJW); Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (JJR); Department of Bio- statistics and Epidemiology, Perelman School of Medicine at the Univer- sity of Pennsylvania, Philadelphia, Pennsylvania (LY); Department of Neurosurgery, Temple University School of Medicine, Philadelphia, Pennsylvania (TMF); Department of Pathology and Laboratory Medicine, Children s Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California (JAB).
authors.forename: Li
authors.initials: L
authors.lastname: Yimei
authors.affiliation: From the Department of Pediatrics (JJR, AJW), Department of Pathology and Laboratory Medicine (MS), and Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (AJW); Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (JJR); Department of Bio- statistics and Epidemiology, Perelman School of Medicine at the Univer- sity of Pennsylvania, Philadelphia, Pennsylvania (LY); Department of Neurosurgery, Temple University School of Medicine, Philadelphia, Pennsylvania (TMF); Department of Pathology and Laboratory Medicine, Children s Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California (JAB).
authors.forename: Jaclyn A
authors.initials: JA
authors.lastname: Biegel
authors.affiliation: From the Department of Pediatrics (JJR, AJW), Department of Pathology and Laboratory Medicine (MS), and Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (AJW); Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (JJR); Department of Bio- statistics and Epidemiology, Perelman School of Medicine at the Univer- sity of Pennsylvania, Philadelphia, Pennsylvania (LY); Department of Neurosurgery, Temple University School of Medicine, Philadelphia, Pennsylvania (TMF); Department of Pathology and Laboratory Medicine, Children s Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California (JAB). santim@email.chop.edu.
authors.forename: Mariarita
authors.initials: M
authors.lastname: Santi
mesh_terms: D000293:Adolescent; D001254:Astrocytoma / Q000235:genetics*; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D017354:Point Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D015514:Oncogene Proteins, Fusion; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; KIAA1549; Pediatric brain tumor; Pilocytic astrocytoma; Pilomyxoid astrocytoma; Single-nucleotide polymorphism (SNP) array.