Subtype-specific expression and genetic alterations of the chemokinereceptor gene CXCR4 in medulloblastomas
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Subtype-specific expression and genetic alterations of the chemokinereceptor gene CXCR4 in medulloblastomas. / Schüller, Ulrich; Koch, Arend; Hartmann, Wolfgang; Garrè, Maria Luisa; Goodyer, Cynthia G; Cama, Armando; Sörensen, Niels; Wiestler, Otmar D; Pietsch, Torsten.
in: INT J CANCER, Jahrgang 117, Nr. 1, 20.10.2005, S. 82-9.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Subtype-specific expression and genetic alterations of the chemokinereceptor gene CXCR4 in medulloblastomas
AU - Schüller, Ulrich
AU - Koch, Arend
AU - Hartmann, Wolfgang
AU - Garrè, Maria Luisa
AU - Goodyer, Cynthia G
AU - Cama, Armando
AU - Sörensen, Niels
AU - Wiestler, Otmar D
AU - Pietsch, Torsten
N1 - Copyright (c) 2005 Wiley-Liss, Inc.
PY - 2005/10/20
Y1 - 2005/10/20
N2 - Recent findings indicate that the chemokine receptor Cxcr4 is essential for normal development of the cerebellar cortex. As medulloblastomas (MBs), the most common malignant brain tumors of childhood, are believed to arise from neuronal cerebellar precursors, we asked whether there is a potential role for Cxcr4 in the pathogenesis of MB. RT-PCR and immunohistochemistry revealed expression of Cxcr4 in different variants of MBs. Whereas 18/20 classic MBs showed very low levels of CXCR4 mRNA, high amounts were expressed in 17/18 desmoplastic and 6/7 extensively nodular MBs. In addition, a significant correlation of high CXCR4 mRNA levels and presence of the neurotrophin receptor p75NTR or expression of ATOH1 and GLI1 suggests that CXCR4 is a reliable marker for tumors derived from the cerebellar external granular layer. Because Cxcr4 is important for migration and cell cycle control of granular precursors, we screened for mutations in the coding region by SSCP and gene sequencing. In a series of 90 MBs and 8 MB cell lines, we found one germline and one somatic mutation resulting in amino acid substitutions in the first (Ile53Leu) and second (Asp97Asn) transmembrane regions, respectively. These data suggest that Cxcr4 may be involved in the pathogenesis of MBs.
AB - Recent findings indicate that the chemokine receptor Cxcr4 is essential for normal development of the cerebellar cortex. As medulloblastomas (MBs), the most common malignant brain tumors of childhood, are believed to arise from neuronal cerebellar precursors, we asked whether there is a potential role for Cxcr4 in the pathogenesis of MB. RT-PCR and immunohistochemistry revealed expression of Cxcr4 in different variants of MBs. Whereas 18/20 classic MBs showed very low levels of CXCR4 mRNA, high amounts were expressed in 17/18 desmoplastic and 6/7 extensively nodular MBs. In addition, a significant correlation of high CXCR4 mRNA levels and presence of the neurotrophin receptor p75NTR or expression of ATOH1 and GLI1 suggests that CXCR4 is a reliable marker for tumors derived from the cerebellar external granular layer. Because Cxcr4 is important for migration and cell cycle control of granular precursors, we screened for mutations in the coding region by SSCP and gene sequencing. In a series of 90 MBs and 8 MB cell lines, we found one germline and one somatic mutation resulting in amino acid substitutions in the first (Ile53Leu) and second (Asp97Asn) transmembrane regions, respectively. These data suggest that Cxcr4 may be involved in the pathogenesis of MBs.
KW - Adolescent
KW - Adult
KW - Amino Acid Substitution
KW - Basic Helix-Loop-Helix Transcription Factors
KW - Cerebellar Neoplasms
KW - Child
KW - Child, Preschool
KW - DNA
KW - DNA Mutational Analysis
KW - DNA-Binding Proteins
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Infant
KW - Medulloblastoma
KW - Middle Aged
KW - Mutation
KW - Nerve Tissue Proteins
KW - Oncogene Proteins
KW - Polymorphism, Single-Stranded Conformational
KW - RNA
KW - RNA, Messenger
KW - Receptor, Nerve Growth Factor
KW - Receptors, CXCR4
KW - Receptors, Nerve Growth Factor
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Trans-Activators
KW - Transcription Factors
KW - Tumor Cells, Cultured
KW - Zinc Finger Protein GLI1
KW - Comparative Study
KW - Journal Article
KW - Multicenter Study
KW - Research Support, Non-U.S. Gov't
U2 - 10.1002/ijc.21116
DO - 10.1002/ijc.21116
M3 - SCORING: Journal article
C2 - 15880586
VL - 117
SP - 82
EP - 89
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 1
ER -