PMID- 9892199
OWN - NLM
STAT- MEDLINE
DCOM- 19990204
LR  - 20061115
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 1
DP  - 1999 Jan 1
TI  - Comprehensive and definitive molecular cytogenetic characterization of HeLa cells 
      by spectral karyotyping.
PG  - 141-50
AB  - We revisited the cytogenetic alterations of the cervical adenocarcinoma cell line 
      HeLa through the use of spectral karyotyping (SKY), comparative genomic 
      hybridization (CGH), and fluorescence in situ hybridization (FISH). SKY analysis 
      unequivocally characterized all abnormal chromosomes. Chromosomal breakpoints 
      were primarily assigned by simultaneous assessment of SKY painted chromosomes and 
      inverted 4,6-diamidino2-phenylindole banding from the same cell. Twenty clonally 
      abnormal chromosomes were found. Comparison with previously reported HeLa 
      G-banding karyotypes revealed a remarkably stable cytogenetic constitution 
      because 18 of 20 markers that were found were present before. The classification 
      of 12 markers was refined in this study. Our assignment of the remaining six 
      markers was consistent with those described in the literature. The CGH map of 
      chromosomal copy number gains and losses strikingly matched the SKY results and 
      was, in a few instances, decisive for assigning breakpoints. The combined use of 
      molecular cytogenetic methods SKY, CGH, and FISH with site-specific probes, in 
      addition to inverted 4,6-diamidino-2-phenylindole or conventional G-banding 
      analysis, provides the means to fully assess the genomic abnormalities in cancer 
      cells. Human papillomaviruses (HPVs) are frequently integrated into the cellular 
      DNA in cervical cancers. We mapped by FISH five HPV18 integration sites: three on 
      normal chromosomes 8 at 8q24 and two on derivative chromosomes, 
      der(5)t(5;22;8)(qll;q11q13;q24) and der(22)t(8; 22)(q24;q13), which have 
      chromosome 8q24 material. An 8q24 copy number increase was detected by CGH. 
      Dual-color FISH with a c-MYC probe mapping to 8q24 revealed colocalization with 
      HPV18 at all integration sites, indicating that dispersion and amplification of 
      the c-MYC gene sequences occurred after and was most likely triggered by the 
      viral insertion at a single integration site. Numerical and structural 
      chromosomal aberrations identified by SKY, genomic imbalances detected by CGH, as 
      well as FISH localization of HPV18 integration at the c-MYC locus in HeLa cells 
      are common and representative for advanced stage cervical cell carcinomas. The 
      HeLa genome has been remarkably stable after years of continuous cultivation; 
      therefore, the genetic alterations detected may have been present in the primary 
      tumor and reflect events that are relevant to the development of cervical cancer.
FAU - Macville, M
AU  - Macville M
AD  - Genome Technology Branch, National Human Genome Research Institute, NIH, 
      Bethesda, Maryland 20892, USA. m.macville@pathol.azn.nl
FAU - Schrock, E
AU  - Schrock E
FAU - Padilla-Nash, H
AU  - Padilla-Nash H
FAU - Keck, C
AU  - Keck C
FAU - Ghadimi, B M
AU  - Ghadimi BM
FAU - Zimonjic, D
AU  - Zimonjic D
FAU - Popescu, N
AU  - Popescu N
FAU - Ried, T
AU  - Ried T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
SB  - IM
MH  - *Chromosome Aberrations
MH  - Cytogenetics/methods
MH  - *HeLa Cells
MH  - Humans
EDAT- 1999/01/19 00:00
MHDA- 1999/01/19 00:01
CRDT- 1999/01/19 00:00
PHST- 1999/01/19 00:00 [pubmed]
PHST- 1999/01/19 00:01 [medline]
PHST- 1999/01/19 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Jan 1;59(1):141-50.