Male-to-female sex ratios of abnormalities detected by fluorescence in situ hybridization in a population of chronic lymphocytic leukemia patients

  • Eduardo S. Cantú | cantue@labcorp.com Integrated Oncology, LabCorp Specialty Testing Group, Phoenix, AZ, United States.
  • John R. McGill Miraca Life Sciences, Phoenix, AZ, United States.
  • Christine F. Stephenson Hematologics, Inc. Seattle, WA, United States.
  • Heidi M. Hoffmann Integrated Genetics, Information Technology, Westborough, MA, United States.
  • Lihua Tang Research and Bioinformatics, Laboratory Corporation of America Holdings, Durham, NC, United States.
  • Jim Yan Research and Bioinformatics, Laboratory Corporation of America Holdings, Durham, NC, United States.
  • Armand B. Glassman Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, SC, United States.

Abstract

Distorted sex ratios occur in hematologic disorders. For example, chronic lymphocytic leukemia (CLL) displays disproportionate sex ratios with a large male excess. However, the underlying genetics for these disparities are poorly understood, and gender differences for specific cytogenetic abnormalities have not been carefully investigated. We sought to provide an initial characterization of gender representation in genetic abnormalities in CLL by using fluorescence in situ hybridization (FISH). We confirm the well known skewed male-to-female (M/F sex ratio) of ~1.5 in our CLL study population, but also determine the genotypic M/F sex ratio values corresponding to specific FISH DNA probes. Genetic changes in CLL detectable by four FISH probes were statistically compared with respect to gender. Initial FISH evaluations of 4698 CLL patients were retrospectively examined and new findings of the genotypic M/F sex ratios for these probes are reported. This study represents the largest CLL survey conducted in the United States using FISH probes. The CLL database demonstrated that FISH abnormalities (trisomy 12, 13q14.3 deletion and 17p13.1 deletion) probes had skewed M/F ratios of ~1.5. Also, by statistical analysis it was shown that ATM gene loss (11q22.3q23.1 deletion) solely or with other abnormalities was considerably higher in males with an M/F ratio of 2.5 and significantly different from M/F ratios of 1.0 or 1.5. We hypothesize that interactions involving these autosomal abnormalities (trisomy 12, and deletions of 11q22.3, 13q14.3, and 17p13.1), and the sex chromosomes may provide the genetic basis for the altered phenotypic M/F ratio in CLL.

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Published
2013-02-11
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Section
Original Articles
Keywords:
sex ratios, CLL, FISH
Statistics
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How to Cite
CantúE. S., McGill, J. R., Stephenson, C. F., Hoffmann, H. M., Tang, L., Yan, J., & Glassman, A. B. (2013). Male-to-female sex ratios of abnormalities detected by fluorescence in situ hybridization in a population of chronic lymphocytic leukemia patients. Hematology Reports, 5(1), e4. https://doi.org/10.4081/hr.2013.e4