Conventional and Array-Based Comparative Genomic Hybridization Analyses of Novel Cell Lines Harboring HPV18 From Glassy Cell Carcinoma of the Uterine Cervix

Int J Oncol. 2004 Apr;24(4):977-86.

Abstract

We established 2 novel human cell lines (GCCOT-1, GCCRK) from glassy cell carcinoma. Both cell lines showed dual tendencies of glandular and squamous differentiation, and thus possess the characteristics resembling reserve cells, the putative origin of most carcinomas arising from the uterine cervix. HPV type 18 DNA including E6-E7, which is commonly found in cell types other than squamous cell carcinoma of uterine cervix, was detected in both cell lines. We analyzed gene copy number alterations of the 2 cell lines using conventional comparative genomic hybridization (CGH) coupled with array-based CGH. Among the putative oncogenes demonstrating copy number gain in both cell lines, FGR(SRC2) at 1p36.2-1 and LAMC2 at 1q25-31 have not been reported to show amplification in previous analyses of conventional cervical cell lines. These oncogenes are thus speculated to be directly associated with oncogenesis of glassy cell carcinoma. On the other hand, among the putative suppressor genes demonstrating copy number loss in both cell lines, the 9q region, ATM at 11q22.3, and CYLD at 16q12-13 have not been reported to show loss in conventional cervical cancer cell lines. These sites are speculated to be important as tumor suppressors directly associated with oncogenesis of glassy cell carcinoma. This study suggests for the first time that together with the presence of HPV type 18, alterations at the above sites are closely associated with oncogenesis of glassy cell carcinoma, a special type of carcinoma in the uterine cervix.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ataxia Telangiectasia Mutated Proteins
  • Carcinoma, Adenosquamous / genetics
  • Carcinoma, Adenosquamous / pathology
  • Carcinoma, Adenosquamous / virology*
  • Cell Cycle Proteins
  • Chromosome Aberrations
  • DNA Probes, HPV
  • DNA, Neoplasm / genetics
  • DNA, Viral / analysis
  • DNA-Binding Proteins*
  • Deubiquitinating Enzyme CYLD
  • Female
  • Gene Dosage
  • Humans
  • Karyotyping
  • Laminin / genetics
  • Nucleic Acid Hybridization*
  • Oligonucleotide Array Sequence Analysis
  • Oncogene Proteins, Viral / genetics*
  • Oncogene Proteins, Viral / metabolism
  • Papillomaviridae / genetics
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / genetics
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins / genetics
  • Uterine Neoplasms / genetics
  • Uterine Neoplasms / pathology
  • Uterine Neoplasms / virology*
  • src-Family Kinases

Substances

  • Cell Cycle Proteins
  • DNA Probes, HPV
  • DNA, Neoplasm
  • DNA, Viral
  • DNA-Binding Proteins
  • E7 protein, Human papillomavirus type 18
  • LAMC2 protein, human
  • Laminin
  • Oncogene Proteins, Viral
  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins
  • Protein-Tyrosine Kinases
  • proto-oncogene proteins c-fgr
  • src-Family Kinases
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases
  • CYLD protein, human
  • Deubiquitinating Enzyme CYLD