[2138] Whole Genome SNP Array Analysis Is Complementary to Classical Cytogenetic Analysis in the Evaluation of Lymphoid Proliferations

Sarah E Gibson, Jianhua Luo, Malini Sathanoori, Rahul Parikh, George K Michalopoulos, Steven H Swerdlow. University of Pittsburgh School of Medicine, Pittsburgh, PA

Background: Cytogenetic evaluation of lymphoid proliferations in clinical practice relies primarily on directed FISH studies and, for a more global analysis, classical cytogenetic karyotypes (CCG). More recently, array CGH and single nucleotide polymorphism (SNP) array analyses have been used to demonstrate additional clinically relevant abnormalities. However, whether these high throughput platforms could replace CCG in the assessment of numerical chromosomal abnormalities is uncertain.
Design: After excluding 4 cases with inadequate DNA, 27 frozen lymph node and related tissue samples with available CCG studies (6 benign, 8 follicular lymphomas, 7 diffuse large B-cell lymphomas, 6 other B-cell lymphomas [ML]) were analyzed using the Genome-Wide Human SNP Array 6.0 (Affymetrix, Santa Clara, CA) and Partek Genomics Suite (Partek, St. Louis, MO). Normal copy number variations were excluded using the Database of Genomic Variants. A benign nasopharyngeal biopsy with numerous unexplained copy number alterations (CNA) and normal CCG was excluded from further analyses.
Results: 9/26 cases (5 ML, 4 benign) had a normal karyotype with CCG and SNP analysis. 8/26 cases (all ML) were partially concordant -- 1 had CNA and balanced translocations by CCG not seen with SNP analysis, 2 had additional CNA by SNP analysis, and 5 had additional, non-overlapping abnormalities by SNP analysis and CCG. 9/26 cases (8 ML, 1 benign) were discordant -- 6 had CNA by CCG not seen with SNP array, including 4 cases also with balanced translocations, and 3 cases had non-overlapping CNA by CCG and SNP analysis. SNP analysis confirmed whole chromosome gains or losses detected on CCG in 2/16 cases, and partially identified whole chromosome abnormalities in 6/16 cases. The remaining 8 discrepant cases had 55.6±31.9% abnormal metaphases. In 5 cases SNP analysis helped to clarify selected CCG findings. Deletion 6q23.3 and gain of 17q23.1-q23.2, seen in 2 ML each, were the most common additional abnormalities detected by SNP analysis.
Conclusions: Whereas SNP analysis provided information not apparent by CCG in 10 cases, CCG provided CNA data not seen in SNP analysis in 15 cases, as well as identifying balanced translocations in 11 cases. Therefore, while SNP analysis provides additional information and can help to clarify CCG findings, CCG studies remain of great utility in identifying global CNA in addition to demonstrating chromosomal translocations. Additional investigations are required to improve high throughput cytogenetic strategies and for validation of SNP array findings.
Category: Techniques

Monday, March 19, 2012 1:00 PM

Poster Session II # 286, Monday Afternoon


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