1: J Neurooncol. 2001 Apr;52(2):119-28. 

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

Krex D, Mohr B, Hauses M, Ehninger G, Schackert HK, Schackert G.

Department of Neurosurgery, University of Technology, Dresden, Germany.

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.

PMID: 11508811 [PubMed - indexed for MEDLINE]


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