Integrated high-resolution array CGH and SKY analysis of homozygous deletions and other genomic alterations present in malignant mesothelioma cell lines

Geula Klorin, Ester Rozenblum, Oleg Glebov, Robert L. Walker, Yoonsoo Park, Paul S. Meltzer, Ilan R. Kirsch, Frederic J. Kaye, Anna V. Roschke

Research output: Contribution to journalArticlepeer-review

Abstract

High-resolution oligonucleotide array comparative genomic hybridization (aCGH) and spectral karyotyping (SKY) were applied to a panel of malignant mesothelioma (MMt) cell lines. SKY has not been applied to MMt before, and complete karyotypes are reported based on the integration of SKY and aCGH results. A whole genome search for homozygous deletions (HDs) produced the largest set of recurrent and non-recurrent HDs for MMt (52 recurrent HDs in 10 genomic regions; 36 non-recurrent HDs). For the first time, LINGO2, RBFOX1/A2BP1, RPL29, DUSP7, and CCSER1/FAM190A were found to be homozygously deleted in MMt, and some of these genes could be new tumor suppressor genes for MMt. Integration of SKY and aCGH data allowed reconstruction of chromosomal rearrangements that led to the formation of HDs. Our data imply that only with acquisition of structural and/or numerical karyotypic instability can MMt cells attain a complete loss of tumor suppressor genes located in 9p21.3, which is the most frequently homozygously deleted region. Tetraploidization is a late event in the karyotypic progression of MMt cells, after HDs in the 9p21.3 region have already been acquired.

Original languageEnglish
Pages (from-to)191-205
Number of pages15
JournalCancer genetics
Volume206
Issue number5
DOIs
StatePublished - May 2013
Externally publishedYes

Keywords

  • Homozygous deletions
  • Malignant mesothelioma
  • Oligonucleotide array CGH
  • Spectral karyotyping
  • Tumor suppressors

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Cancer Research

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