Gene copy number analysis in malignant pleural mesothelioma using oligonucleotide array CGH

Cytogenetic and Genome Research. 2007;119(1-2):46-52. Epub 2007 Dec
14. [Link]

Lindholm PM,
Salmenkivi K, Vauhkonen H, Nicholson AG, Anttila S, Kinnula VL,
Knuutila S.

Department
of Pathology, Haartman Institute and HUSLAB, University of Helsinki and
Helsinki University Central Hospital, Finland.

Abstract

Conventional
cytogenetic analyses and comparative genomic hybridization have
revealed a complex and even chaotic nature of chromosomal aberrations
in pleural malignant mesothelioma (MM). We set out to describe the
complex gene copy number changes and screen for novel genetic
aberrations using a high-density oligonucleotide microarray platform
for comparative genomic hybridization (aCGH) of a series of 26
well-characterized MM tumor samples. The number of copy number changes
varied from zero to 40 per sample. Gene copy number losses predominated
over gains, and the most frequent region of loss was 9p21.3 (17/26
cases), the locus of CDKN2A and CDKN2B, both known to be commonly lost
in MM. The most recurrent minimal regions of losses were
1p31.1–>
p13.2, 3p22.1–>p14.2, 6q22.1, 9p21.3, 13cen–>q14.12,
14q22.1–>qter, and 22qcen–>q12.3. Previously unreported
gains
included 9p13.3, 7p22.3–>p22.2, 12q13.3, and
17q21.32–>qter.
The results suggest that gene copy number losses are a major mechanism
of MM carcinogenesis and reveal a recurrent pattern of copy number
changes in MM.