Identification of uncommon chromosomal aberrations in the neuroglioma cell line H4 by spectral karyotyping

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • D. Krex - , Klinik und Poliklinik für Neurochirurgie (Autor:in)
  • B. Mohr - , Medizinische Klinik und Poliklinik I, Technische Universität Dresden (Autor:in)
  • M. Hauses - , Technische Universität Dresden (Autor:in)
  • G. Ehninger - , Technische Universität Dresden (Autor:in)
  • H. K. Schackert - , Technische Universität Dresden (Autor:in)
  • G. Schackert - , Technische Universität Dresden (Autor:in)

Abstract

To elucidate the reasons why mRNA expression of the LGI1 candidate tumor-suppressor gene was severely reduced in the glioma-derived cell line H4, as demonstrated in a previous study, we performed a cytogenetic analysis of this cell line using conventional methods and fluorescence in situ hybridization (FISH) techniques [spectral karyotyping (SKY), interphase- and chromosome FISH of metaphases (I- and C-FISH)]. Cell line H4 is monoclonal and near triploid (±3n). SKY enabled us to detect 24 structural aberrations: unbalanced translocations, n = 12; deletions, n = 10; insertion, n = 1; duplication, n = 1. The results were confirmed by I- and C-FISH analysis using chromosome-specific paints, centromer-specific probes and locus-specific probes for p53, PTEN/MMAC1, LGI1, Cyclin D1, EGR1, ETV6/TEL, AML1, and the genomic region 13q14.3 containing the Rb locus. We found loss of one copy of p53 as well as of one copy of Rb. Complete loss of PTEN/MMAC1 was detected, while all copies of LGI1 and Cyclin D1 were preserved. Interestingly, there was a gain of ETV6/TEL and EGR1, which were each present in quadruplicate. Additionally, the AML1 locus revealed mosaicism of cells with three and four copies, respectively. Additionally, a 5q-chromosome [del(5)(q13q33)] was found, which is one of the common features in hematological malignancies, and der(12)t(1;12) was found, suggesting that there might be an additional ETV6/TEL fusion protein. The combination of SKY, I- and C-FISH demonstrates that the neuroglioma cell line H4 harbors cytogenetic aberrations that are reported to occur in glioma-derived cell lines and additional chromosomal aberrations that have so far not been reported to occur in these cell lines. The complex aberrant karyotype and possibly generation of transcription factors by fusion proteins might be reasons for the impaired mRNA expression of the LGI1 candidate tumor-suppressor gene in cell line H4.

Details

OriginalspracheEnglisch
Seiten (von - bis)119-128
Seitenumfang10
FachzeitschriftJournal of neuro-oncology
Jahrgang52
Ausgabenummer2
PublikationsstatusVeröffentlicht - 2001
Peer-Review-StatusJa

Externe IDs

PubMed 11508811

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Glioma pathogenesis, Glioma-derived cell line, Neuroglioma, Spectral karyotyping