Challenges in array comparative genomic hybridization for the analysis of cancer samples

Area of Science:

• Genomics
• Cancer Research
• Molecular Diagnostics

Background:

• Array comparative genomic hybridization (aCGH) is a powerful tool for detecting genomic copy number alterations.
• Clinical integration of aCGH faces challenges including DNA quality, tissue heterogeneity, and platform variability.

Purpose of the Study:

• To evaluate the feasibility of aCGH for clinical use with challenging samples.
• To compare the performance of bacterial artificial chromosome (BAC) and oligonucleotide (Agilent) aCGH platforms.

Main Methods:

• Assessed impact of DNA source (archival), quantity, and amplification on aCGH results.
• Employed microdissection techniques to isolate tumor cells and minimize heterogeneity.
• Compared performance of BAC and Agilent aCGH platforms using various datasets.

Main Results:

• aCGH detected copy number alterations in DNA from as few as 100 microdissected cells.
• Whole genome amplification did not introduce significant allele bias.
• BAC aCGH platforms showed greater concordance and less technical noise than Agilent platforms.

Conclusions:

• aCGH can robustly detect copy number alterations in challenging tumor samples, including archival and low-yield DNA.
• BAC aCGH platforms provide more reliable data interpretation due to fewer outliers compared to oligonucleotide platforms.