TY - JOUR
T1 - Microarray-based genomic profiling as a diagnostic tool in acute lymphoblastic leukemia
AU - Simons, Annet
AU - Stevens-Kroef, Marian
AU - El Idrissi-Zaynoun, Najat
AU - van Gessel, Sabine
AU - Weghuis, Daniel Olde
AU - van den Berg, Eva
AU - Waanders, Esmé
AU - Hoogerbrugge, Peter
AU - Kuiper, Roland
AU - van Kessel, Ad Geurts
N1 - Copyright © 2011 Wiley Periodicals, Inc.
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
KW - Child
KW - Chromosome Aberrations
KW - DNA Fingerprinting/methods
KW - Female
KW - Gene Dosage
KW - Humans
KW - In Situ Hybridization, Fluorescence/methods
KW - Karyotyping/methods
KW - Male
KW - Oligonucleotide Array Sequence Analysis/methods
KW - Polymorphism, Single Nucleotide
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis
KW - Sensitivity and Specificity
U2 - 10.1002/gcc.20919
DO - 10.1002/gcc.20919
M3 - Article
C2 - 21882283
SN - 1045-2257
VL - 50
SP - 969
EP - 981
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
IS - 12
ER -