Array Comparative Genomic Hybridization: Impact in the Assessment of Plasma Cell Myeloma Genetic Profile and Prognosis

Abstract 4965

Identification of specific chromosomal alterations in plasma cell myeloma (PCM) is essential for the prognosis and treatment of this disease. Although cytogenetic chromosome and fluorescence in situ hybridization (FISH) analyses are techniques currently used for this purpose, incorporation of array comparative genomic hybridization (aCGH) analysis as described in this study, demonstrates the insufficient power of traditional techniques in characterizing the complex and heterogeneous genetic profile of this group of hematological malignancies. In our cohort, aCGH study of 500 diagnosed PCM patients identified clinically significant genomic alterations in 56% of cases compared to 22% and 32% by chromosome and FISH analyses, respectively. Important findings by aCGH include the presence of hyperdiploid chromosome complement (15 > 9 > 5 > 19 > 11 > 3 > 7 > 21 > 6 > 18 >14) in 35% of cases which is associated with a favorable prognosis, as well as adverse prognostic markers such as hypodiploid chromosome complement (13 > Y >14 > 22> 10 >16 >8), gain of genetic material in chromosome 1q (CKS1B, PDZK1, ANP32E) and losses in chromosomes 1p (CDKN2C, FAM46C), 6q (PRDM1), 12p (ETV6, CDKN1B), and 17p (TP53) observed in 25% of patients. Recurrent alterations identified in 9% of cases only by aCGH include extra copies of genes which could be potentially poor prognostic indicators such as IRF4 (6p25. 3, transactivates MYC oncogene), IL-6 (7p15. 3, growth factor), BRAF (7q34, regulating the MAP kinase/ERKs signaling pathway), CYLC2 (9q31. 1, active cyclin in cell cycle progression from G1 to S phase), and genes located in the telomeric region of chromosome Xq. The results obtained in this study demonstrate the superior resolution and detection rate of aCGH technology in understanding the genetic heterogeneity of PCM as well as the importance of incorporating this methodology into current algorithms for the diagnosis and prognosis of plasma cell disorders.