Copyright © 2000 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 66, Issue 5, 1516-1521, 1 May 2000
doi:10.1086/302878
Comparative Genomic Hybridization in Combination with Flow Cytometry Improves Results of Cytogenetic Analysis of Spontaneous Abortions
Brenda Lomax1, Steven Tang1, Evica Separovic1, Don Phillips2, E. Hillard2, Tom Thomson2 and Dagmar K. Kalousek1, 
, 
1 Department of Pathology and Laboratory Medicine, University of British Columbia, and British Columbia Research Institute for Children’s and Women’s Health, Vancouver
2 Department of Laboratory Medicine, Analytic Cytology Department, British Columbia Cancer Agency, Vancouver
Address for correspondence and reprints: Dr. Dagmar K. Kalousek, British Columbia Children’s and Women’s Hospital, 4480 Oak Street, Vancouver, B.C., Canada V6H 3V4Abstract
More than 50% of spontaneous abortions (SAs) have abnormal chromosomes; the most common abnormalities are trisomy, sex chromosome monosomy, and polyploidy. Conventional cytogenetic analysis of SAs depends on tissue culturing and is associated with a significant tissue culture failure rate and contamination by maternally derived cells. Comparative genomic hybridization (CGH), in combination with flow cytometry (FCM), can detect numerical and unbalanced structural chromosomal abnormalities associated with SAs while avoiding the technical problems associated with tissue culture. Routine cytogenetic and CGH analysis was performed independently on tissue from 301 SAs. Samples shown to be chromosomally balanced by CGH were analyzed by FCM to determine ploidy. Of 253 samples successfully analyzed by both approaches, there was an absolute correlation of results in 235 (92.8%). Of the 18 cases with discrepancies between cytogenetic and CGH/FCM results, an explanation could be found in 17. Twelve samples produced a 46,XX karyotype by cytogenetics, whereas CGH/FCM demonstrated aneuploidy/polyploidy or a male genome, indicating maternal contamination of the tissue cultures. In two cases, where tetraploidy was demonstrated by cytogenetics and diploidy by FCM, tissue culture artifact is implied. In three cases, CGH demonstrated an aneuploidy, and cytogenetics demonstrated hypertriploidy. In one unexplainable case, aneuploidy demonstrated by CGH could not be detected by repeat CGH analysis, conventional cytogenetic, or FISH analysis. These results demonstrate that CGH supplemented with FCM can readily identify chromosomal abnormalities associated with SAs and, by avoiding maternal contamination and tissue culture artifacts, can do so with a lower failure rate and more accuracy than conventional cytogenetic analysis.
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