title: Microarray-based genomic profiling as a diagnostic tool in acute lymphoblastic leukemia.
abstract: In acute lymphoblastic leukemia (ALL) specific genomic abnormalities provide important clinical information. In most routine clinical diagnostic laboratories conventional karyotyping, in conjunction with targeted screens using e.g., fluorescence in situ hybridization (FISH), is currently considered as the gold standard to detect such aberrations. Conventional karyotyping, however, is limited in its resolution and yield, thus hampering the genetic diagnosis of ALL. We explored whether microarray-based genomic profiling would be feasible as an alternative strategy in a routine clinical diagnostic setting. To this end, we compared conventional karyotypes with microarray-deduced copy number aberration (CNA) karyotypes in 60 ALL cases. Microarray-based genomic profiling resulted in a CNA detection rate of 90%, whereas for conventional karyotyping this was 61%. In addition, many small (< 5 Mb) genetic lesions were encountered, frequently harboring clinically relevant ALL-related genes such as CDKN2A/B, ETV6, PAX5, and IKZF1. From our data we conclude that microarray-based genomic profiling serves as a robust tool in the genetic diagnosis of ALL, outreaching conventional karyotyping in CNA detection both in terms of sensitivity and specificity. We also propose a practical workflow for a comprehensive and objective interpretation of CNAs obtained through microarray-based genomic profiling, thereby facilitating its application in a routine clinical diagnostic setting.
authors: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Radboud University Centre for Oncology, Nijmegen, The Netherlands. a.simons@antrg.umcn.nl
authors: Annet
authors: A
authors: Simons
authors: Marian
authors: M
authors: Stevens-Kroef
authors: Najat
authors: N
authors: El Idrissi-Zaynoun
authors: Sabine
authors: S
authors: van Gessel
authors: Daniel Olde
authors: DO
authors: Weghuis
authors: Eva
authors: E
authors: van den Berg
authors: Esmé
authors: E
authors: Waanders
authors: Peter
authors: P
authors: Hoogerbrugge
authors: Roland
authors: R
authors: Kuiper
authors: Ad Geurts
authors: AG
authors: van Kessel
mesh_terms: D002648:Child; D002869:Chromosome Aberrations; D016172:DNA Fingerprinting / Q000379:methods; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007621:Karyotyping / Q000379:methods; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics*; D012680:Sensitivity and Specificity