Journal Article

Chromosome-wide aneuploidy study (CWAS) in workers exposed to an established leukemogen, benzene

Luoping Zhang, Qing Lan, Weihong Guo, Alan E. Hubbard, Guilan Li, Stephen M. Rappaport, Cliona M. McHale, Min Shen, Zhiying Ji, Roel Vermeulen, Songnian Yin, Nathaniel Rothman and Martyn T. Smith

in Carcinogenesis

Volume 32, issue 4, pages 605-612
Published in print April 2011 | ISSN: 0143-3334
Published online January 2011 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgq286
Chromosome-wide aneuploidy study (CWAS) in workers exposed to an established leukemogen, benzene

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Evidence suggests that de novo, therapy-related and benzene-induced acute myeloid leukemias (AML) occur via similar cytogenetic and genetic pathways, several of which involve aneuploidy, the loss or gain of chromosomes. Aneuploidy of specific chromosomes has been detected in benzene-related leukemia patients as well as in healthy benzene-exposed workers, suggesting that aneuploidy precedes and may be a potential mechanism underlying benzene-induced leukemia. Here, we analyzed the peripheral blood lymphocytes of 47 exposed workers and 27 unexposed controls using a novel OctoChrome fluorescence in situ hybridization (FISH) technique that simultaneously detects aneuploidy in all 24 chromosomes. Through this chromosome-wide aneuploidy study (CWAS) approach, we found heterogeneity in the monosomy and trisomy rates of the 22 autosomes when plotted against continuous benzene exposure. In addition, statistically significant, chromosome-specific increases in the rates of monosomy [5, 6, 7, 10, 16 and 19] and trisomy [5, 6, 7, 8, 10, 14, 16, 21 and 22] were found to be dose dependently associated with benzene exposure. Furthermore, significantly higher rates of monosomy and trisomy were observed in a priori defined ‘susceptible’ chromosome sets compared with all other chromosomes. Together, these findings confirm that benzene exposure is associated with specific chromosomal aneuploidies in hematopoietic cells, which suggests that such aneuploidies may play roles in benzene-induced leukemogenesis.

Journal Article.  5440 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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