title: Cytogenetic landscape of paired neurospheres and traditional monolayer cultures in pediatric malignant brain tumors.
abstract: BACKGROUND
  New therapeutic targets are needed to eliminate cancer stem cells (CSCs). We hypothesize that direct comparison of paired CSCs and nonstem tumor cells (NSTCs) will facilitate identification of primary "driver" chromosomal aberrations that can serve as diagnostic markers and/or therapeutic targets.
  
  
  METHODS
  We applied spectral karyotyping and G-banding to matched pairs of neurospheres (CSC-enriched cultures) and fetal bovine serum-based monolayer cultures (enriched with NSTCs) from 16 patient-derived orthotopic xenograft mouse models, including 9 medulloblastomas (MBs) and 7 high-grade gliomas (HGGs), followed by direct comparison of their numerical and structural abnormalities.
  
  
  RESULTS
  Chromosomal aberrations were detected in neurospheres of all 16 models, and 82.0% numerical and 82.4% structural abnormalities were maintained in their matching monolayer cultures. Among the shared abnormalities, recurrent clonal changes were identified including gain of chromosomes 18 and 7 and loss of chromosome 10/10q (5/16 models), isochromosome 17q in 2 MBs, and a new breakpoint of 13q14 in 3 HGGs. Chromothripsis-like evidence was also observed in 3 HGG pairs. Additionally, we noted 20 numerical and 15 structural aberrations that were lost from the neurospheres and found 26 numerical and 23 structural aberrations that were only present in the NSTCs. Compared with MBs, the neurosphere karyotypes of HGG were more complex, with fewer chromosomal aberrations preserved in their matching NSTCs.
  
  
  CONCLUSIONS
  Self-renewing CSCs in MBs and pediatric HGGs harbor recurrent numerical and structural aberrations that were maintained in the matching monolayer cultures. These primary chromosomal changes may represent new markers for anti-CSC therapies.
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (X.Z., Q.L., L.Y., Z.L., H.L., M.K., X.-N.L.); Molecular Cytogenetics, Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (Y.-J.Z., P.R., X.L.); Laboratory of Clinical Cytogenetics, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (X.L.).
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (X.Z., Q.L., L.Y., Z.L., H.L., M.K., X.-N.L.); Molecular Cytogenetics, Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (Y.-J.Z., P.R., X.L.); Laboratory of Clinical Cytogenetics, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (X.L.).
authors.forename: Yi-Jue
authors.initials: YJ
authors.lastname: Zhao
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (X.Z., Q.L., L.Y., Z.L., H.L., M.K., X.-N.L.); Molecular Cytogenetics, Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (Y.-J.Z., P.R., X.L.); Laboratory of Clinical Cytogenetics, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (X.L.).
authors.forename: Qi
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (X.Z., Q.L., L.Y., Z.L., H.L., M.K., X.-N.L.); Molecular Cytogenetics, Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (Y.-J.Z., P.R., X.L.); Laboratory of Clinical Cytogenetics, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (X.L.).
authors.forename: Litian
authors.initials: L
authors.lastname: Yu
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (X.Z., Q.L., L.Y., Z.L., H.L., M.K., X.-N.L.); Molecular Cytogenetics, Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (Y.-J.Z., P.R., X.L.); Laboratory of Clinical Cytogenetics, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (X.L.).
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (X.Z., Q.L., L.Y., Z.L., H.L., M.K., X.-N.L.); Molecular Cytogenetics, Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (Y.-J.Z., P.R., X.L.); Laboratory of Clinical Cytogenetics, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (X.L.).
authors.forename: Holly
authors.initials: H
authors.lastname: Lindsay
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (X.Z., Q.L., L.Y., Z.L., H.L., M.K., X.-N.L.); Molecular Cytogenetics, Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (Y.-J.Z., P.R., X.L.); Laboratory of Clinical Cytogenetics, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (X.L.).
authors.forename: Mari
authors.initials: M
authors.lastname: Kogiso
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (X.Z., Q.L., L.Y., Z.L., H.L., M.K., X.-N.L.); Molecular Cytogenetics, Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (Y.-J.Z., P.R., X.L.); Laboratory of Clinical Cytogenetics, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (X.L.).
authors.forename: Pulivarthi
authors.initials: P
authors.lastname: Rao
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (X.Z., Q.L., L.Y., Z.L., H.L., M.K., X.-N.L.); Molecular Cytogenetics, Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (Y.-J.Z., P.R., X.L.); Laboratory of Clinical Cytogenetics, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (X.L.).
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (X.Z., Q.L., L.Y., Z.L., H.L., M.K., X.-N.L.); Molecular Cytogenetics, Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas (Y.-J.Z., P.R., X.L.); Laboratory of Clinical Cytogenetics, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (X.L.).
authors.forename: Xinyan
authors.initials: X
authors.lastname: Lu
mesh_terms: D000293:Adolescent; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics*; D002417:Cattle; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D005260:Female; D005910:Glioma / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000235:genetics*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism; D012710:Serum Albumin, Bovine; D014183:Transplantation, Heterologous
chemical_list: D012710:Serum Albumin, Bovine
keywords: cancer stem cell; chromosomal aberration; neurosphere; orthotopic xenograft model