Detection of low-level mosaicism by array CGH in routine diagnostic specimens

Area of Science:

• Clinical Cytogenetics
• Genomics
• Molecular Diagnostics

Background:

• Microarray-based comparative genomic hybridization (array CGH) offers high-resolution genomic screening.
• The capacity of array CGH to detect low-level mosaicism remains largely uncharacterized.

Purpose of the Study:

• To evaluate the effectiveness of array CGH in detecting low-level mosaicism in a clinical diagnostic setting.
• To compare array CGH findings with traditional cytogenetic methods for mosaicism detection.

Main Methods:

• Analysis of over 3,600 clinical cases using a custom-designed SignatureChip array CGH.
• Fluorescence in situ hybridization (FISH) for confirmation of suspected mosaic chromosome abnormalities.
• Comparison of FISH results from PHA-stimulated and unstimulated peripheral blood cultures.

Main Results:

• Array CGH detected 18 cases of mosaicism, 14 previously unknown (approx. 8% of abnormal cases).
• FISH confirmed mosaic abnormalities including marker chromosomes, trisomies, deletions, and derivative chromosomes.
• Discrepancies in abnormal cell percentages were observed between stimulated and unstimulated blood cultures, with array CGH detecting abnormalities in uncultured DNA.

Conclusions:

• Array CGH is a powerful tool for detecting low-level mosaicism in clinical cytogenetics.
• Traditional cytogenetic analysis of stimulated cultures may underestimate or miss mosaic chromosome abnormalities.
• Array CGH using uncultured genomic DNA offers improved detection of mosaic unbalanced chromosome abnormalities.