title: Centrosome amplification is correlated with ploidy divergence, but not with MYCN amplification, in neuroblastoma tumors.
abstract: Ploidy is an important biologic feature defining heterogeneous neuroblastoma. To clarify whether centrosome amplification is correlated with ploidy status or MYCN amplification, we examined centrosomes by immunostaining, and ploidy and MYCN copy numbers by fluorescence in situ hybridization in 27 neuroblastomas. There were 8 infant triploid, 9 infant diploid, and 10 childhood diploid tumors. Ploidy divergence, defined as a mixed population of cells with trisomy 1, cells with tetrasomy 1, and/or cells with pentasomy 1 in diploid tumors and that of cells with tetrasomy 1 and cells with pentasomy 1 in triploid tumors, each occupying more than 5% of cells, was found in 78% of infant diploid tumors, but not in triploid and childhood diploid tumors (P<0.0001). Childhood and infant diploid tumors had higher incidences of centrosome amplification than infant triploid tumors (P=0.0001 and 0.07, respectively). While both infant and childhood diploid tumors share a high incidence of centrosome amplification, only infant diploid tumors showed ploidy divergence, implying the presence of cytokinesis failure. These findings suggest that centrosome amplification found in cells of infant diploid tumors and that found in cells of childhood diploid tumors may be generated by different mechanisms. MYCN amplification was not correlated with centrosome amplification in sporadic neuroblastomas.
authors.affiliation: Department of Cancer Diagnosis, Research Institute for Clinical Oncology, Saitama Cancer Center, Ina, Saitama 362-0806, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fukushi
authors.forename: Naoki
authors.initials: N
authors.lastname: Watanabe
authors.forename: Fumio
authors.initials: F
authors.lastname: Kasai
authors.forename: Masayuki
authors.initials: M
authors.lastname: Haruta
authors.forename: Akira
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kikuta
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.forename: Hisaya
authors.initials: H
authors.lastname: Nakadate
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tsunematsu
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kaneko
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics; D018385:Centrosome / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005434:Flow Cytometry; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008479:Mediastinal Neoplasms / Q000235:genetics; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011003:Ploidies; D012186:Retroperitoneal Neoplasms / Q000235:genetics
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins