Detection limits of DNA copy number alterations in heterogeneous cell populations.

摘要: Array Comparative Genomic Hybridization (aCGH) is a widely used technique to assess chromosomal copy number alterations. Chromosomal content, however, often not uniform throughout cell populations. Here we evaluated what extent aCGH can detect DNA alterations in heterogeneous A systematic evaluation currently lacking, despite its importance diagnostics and research. The detection limits reported are compound of analytical software laboratory techniques do account for the probes relation sample homogeneity. Detection were explored with isolated from patient intellectual disability (ID) tumor line BT474. Both diluted increasing amounts normal simulate different levels cellularity. Samples hybridized on microarrays containing 180,880 oligonucleotides evenly distributed over genome (spacing ~17 kb). Single alterations, represented by down 249 (4 Mb) present 10 % population, could be detected. Alterations encompassing as few 14 (~238 Kb) also detected, but this 35 % mosaic level was required. detected populations abnormal cells. sub-megabase requires higher percentage cells or probe density.