PB1662 INTEGRATION OF GENOME‐WIDE ANALYSIS INTO CLINICAL DIAGNOSIS OF ACUTE LYMPHOBLASTIC LEUKEMIA: HOW MUCH CAN WE IMPROVE CYTOGENETIC TESTING?

Abstract

Background:Acute lymphoblastic leukemia (ALL) is a heterogeneous, aggressive disease, and most common in children. It is a leading cause of cancer death in young and adult, too. However, about 30% of pediatric and 50% of adult ALL patients still lack defined genetic hallmarks of biological and clinical significance. In addition, complex karyotype‐ALL (CX‐ALL) promoting a wide spectrum of diverse genetic alterations with striking genomic instability, are overall often neglected by research.Aims:The overall goal of this study was to characterize karyotypes and genetic content of 25 ALL cases and to rule out if one single molecular approach may be sufficient to detect genomic aberrations in these patients.Methods:ALL cases were retrospectively studied by multitude multicolor banding (mMCB), fluorescence in situ hybridization (FISH) using selected locus‐specific probes and array‐comparative genomic hybridization (aCGH).Results:Most strikingly, 13 of the studied 25 ALLs (∼55%) revealed abnormal karyotypes, applying mMCB: structural abnormalities were present in 12 and even numerical ones were identified in 2 cases. Overall, 123 copy number alterations (CNAs) were identified as loss (∼80%) or as gains (∼20%). Furthermore, highly complex karyotypes were detected by aCGH and mMCB in 4 out of the 13 aberrant cases. The latter four patients had either deletions or amplifications in genes involved in lymphoid development, cell cycle, Hematopoietic stem cells development and/or DNA repair (IKZF1, CDKN2A/B, PAX5, BIRC3, ATM, RB1, RUNX1), as shown by FISH, and also presented acquired marker chromosomes.Summary/Conclusion:Molecular approaches are suited to identify cryptic aberrations and potential target genes involved in leukemogenesis and progression of the disease. The present work demonstrated that aCGH is a highly efficient tool for detection of CNAs in ALL. However, while aCGH provide data on imbalanced genomic alterations, molecular cytogenetics additionally detects different leukemic subclones within one sample, as well as balanced translocations leading to tumor‐specific fusion genes. Thus, still no single approach is sufficient to comprehensively characterize all acquired aberrations in ALL.