Genome-wide allelic state analysis on flow-sorted tumor fractions provides an accurate measure of chromosomal aberrations.

摘要: Chromosomal aberrations are a common characteristic of cancer and associated with copy number abnormalities loss heterozygosity (LOH). Tumor heterogeneity, low tumor cell percentage, lack knowledge the DNA content impair identification these alterations especially in aneuploid tumors. To accurately detect allelic changes carcinomas, we combined flow-sorting single nucleotide polymorphism arrays. Cells derived from archival cervical colon cancers were flow-sorted based on differential vimentin keratin expression analyzed A new algorithm, lesser allele intensity ratio, was used to generate molecular measure chromosomal for each case. Flow-sorting significantly improved detection abnormalities; 31.8% showed an increase amplitude 23.2% missed unsorted fraction, whereas 15.9% detected but interpreted differently. Integration index analysis enabled state aberrations, such as LOH ([A]), copy-neutral ([AA]), balanced amplifications ([AABB]), imbalances ([AAB] or [AAAB], etc.). segments sharply defined. Fluorescence situ hybridization numbers, well high similarity between index, which is average states across genome, validated method. This approach provides individual will likely have repercussions preoperative staging, classification, prognostic profiling tumors, particularly heterogeneous allows study underlying genetic mechanisms clonal evolution subpopulations. [Cancer Res 2008;68(24):10333–40]