PMID- 25320376 OWN - NLM STAT- MEDLINE DCOM- 20150219 LR - 20190722 IS - 1530-8561 (Electronic) IS - 0009-9147 (Linking) VI - 60 IP - 12 DP - 2014 Dec TI - Detection of clonal evolution in hematopoietic malignancies by combining comparative genomic hybridization and single nucleotide polymorphism arrays. PG - 1558-68 LID - 10.1373/clinchem.2014.227785 [doi] AB - BACKGROUND: Array comparative genomic hybridization (aCGH) has become a powerful tool for analyzing hematopoietic neoplasms and identifying genome-wide copy number changes in a single assay. aCGH also has superior resolution compared with fluorescence in situ hybridization (FISH) or conventional cytogenetics. Integration of single nucleotide polymorphism (SNP) probes with microarray analysis allows additional identification of acquired uniparental disomy, a copy neutral aberration with known potential to contribute to tumor pathogenesis. However, a limitation of microarray analysis has been the inability to detect clonal heterogeneity in a sample. METHODS: This study comprised 16 samples (acute myeloid leukemia, myelodysplastic syndrome, chronic lymphocytic leukemia, plasma cell neoplasm) with complex cytogenetic features and evidence of clonal evolution. We used an integrated manual peak reassignment approach combining analysis of aCGH and SNP microarray data for characterization of subclonal abnormalities. We compared array findings with results obtained from conventional cytogenetic and FISH studies. RESULTS: Clonal heterogeneity was detected in 13 of 16 samples by microarray on the basis of log2 values. Use of the manual peak reassignment analysis approach improved resolution of the sample's clonal composition and genetic heterogeneity in 10 of 13 (77%) patients. Moreover, in 3 patients, clonal disease progression was revealed by array analysis that was not evident by cytogenetic or FISH studies. CONCLUSIONS: Genetic abnormalities originating from separate clonal subpopulations can be identified and further characterized by combining aCGH and SNP hybridization results from 1 integrated microarray chip by use of the manual peak reassignment technique. Its clinical utility in comparison to conventional cytogenetic or FISH studies is demonstrated. CI - (c) 2014 American Association for Clinical Chemistry. FAU - Hartmann, Luise AU - Hartmann L AD - HematoLogics Inc., Seattle, WA. FAU - Stephenson, Christine F AU - Stephenson CF AD - HematoLogics Inc., Seattle, WA. FAU - Verkamp, Stephanie R AU - Verkamp SR AD - HematoLogics Inc., Seattle, WA. FAU - Johnson, Krystal R AU - Johnson KR AD - HematoLogics Inc., Seattle, WA. FAU - Burnworth, Bettina AU - Burnworth B AD - HematoLogics Inc., Seattle, WA. FAU - Hammock, Kelle AU - Hammock K AD - HematoLogics Inc., Seattle, WA. FAU - Brodersen, Lisa Eidenschink AU - Brodersen LE AD - HematoLogics Inc., Seattle, WA. FAU - de Baca, Monica E AU - de Baca ME AD - HematoLogics Inc., Seattle, WA. FAU - Wells, Denise A AU - Wells DA AD - HematoLogics Inc., Seattle, WA. FAU - Loken, Michael R AU - Loken MR AD - HematoLogics Inc., Seattle, WA. FAU - Zehentner, Barbara K AU - Zehentner BK AD - HematoLogics Inc., Seattle, WA. barbara@hematologics.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141015 PL - England TA - Clin Chem JT - Clinical chemistry JID - 9421549 SB - IM MH - Clonal Evolution/*genetics MH - *Comparative Genomic Hybridization MH - Hematologic Neoplasms/*genetics/*pathology MH - Humans MH - *Oligonucleotide Array Sequence Analysis MH - Polymorphism, Single Nucleotide/*genetics EDAT- 2014/10/17 06:00 MHDA- 2015/02/20 06:00 CRDT- 2014/10/17 06:00 PHST- 2014/10/17 06:00 [entrez] PHST- 2014/10/17 06:00 [pubmed] PHST- 2015/02/20 06:00 [medline] AID - clinchem.2014.227785 [pii] AID - 10.1373/clinchem.2014.227785 [doi] PST - ppublish SO - Clin Chem. 2014 Dec;60(12):1558-68. doi: 10.1373/clinchem.2014.227785. Epub 2014 Oct 15.