Evaluation of chronic lymphocytic leukemia by oligonucleotide-based microarray analysis uncovers novel aberrations not detected by FISH or cytogenetic analysis

Cook, Kolquist, Schultz, Slovak, Mcdaniel, Brown, Tubbs, Theil, Cawich Victoria, Valentin Caitlin, Minier Sara, Neill, Byerly Steve, Morton S, Sahoo Trilochan, Ballif, Shaffer

Description

Cytogenetic evaluation is a key component of the diagnosis and prognosis of chronic lymphocytic leukemia (CLL). We performed oligonucleotide-based comparative genomic hybridization microarray analysis on 34 samples with CLL and known abnormal karyotypes previously determined by cytogenetics and/or fluorescence in situ hybridization (FISH). Results Using a custom designed microarray that targets >1800 genes involved in hematologic disease and other malignancies, we identified additional cryptic aberrations and novel findings in 59% of cases. These included gains and losses of genes associated with cell cycle regulation, apoptosis and susceptibility loci on 3p21.31, 5q35.2q35.3, 10q23.31q23.33, 11q22.3, and 22q11.23. Conclusions Our results show that microarray analysis will detect known aberrations, including microscopic and cryptic alterations. In addition, novel genomic changes will be uncovered that may become important prognostic predictors or treatment targets for CLL in the future.

Sujets

• B-cell chronic lymphocytic leukemia
• Microarray
• Oligonucléotide
• Fish
• Cytogenetics
• Chromosome abnormality

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 7
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Kolquist et al . Molecular Cytogenetics 2011, 4 :25 http://www.molecularcytogenetics.org/content/4/1/25

R E S E A R C H Open Access Evaluation of chronic lymphocytic leukemia by oligonucleotide-based microarray analysis uncovers novel aberrations not detected by FISH or cytogenetic analysis Kathryn A Kolquist 1 , Roger A Schultz 2 , Marilyn L Slovak 2,5 , Lisa D McDaniel 1,2 , Theresa C Brown 3 , Raymond R Tubbs 4 , James R Cook 4 , Karl S Theil 4 , Victoria Cawich 2 , Caitlin Valentin 2 , Sara Minier 2 , Nicholas J Neill 2 , Steve Byerly 2 , S Annie Morton 2 , Trilochan Sahoo 2,6 , Blake C Ballif 2 and Lisa G Shaffer 2*

Abstract Background: Cytogenetic evaluation is a key component of the diagnosis and prognosis of chronic lymphocytic leukemia (CLL). We performed oligonucleotide-based comparative genomic hybridization microarray analysis on 34 samples with CLL and known abnormal karyotypes previously determined by cytogenetics and/or fluorescence in situ hybridization (FISH). Results: Using a custom designed microarray that targets >1800 genes involved in hematologic disease and other malignancies, we identified additional cryptic aberrations and novel findings in 59% of cases. These included gains and losses of genes associated with cell cycle regulation, apoptosis and susceptibility loci on 3p21.31, 5q35.2q35.3, 10q23.31q23.33, 11q22.3, and 22q11.23. Conclusions: Our results show that microarray analysis will detect known aberrations, including microscopic and cryptic alterations. In addition, novel genomic changes will be uncovered that may become important prognostic predictors or treatment targets for CLL in the future. Keywords: chronic lymphocytic leukemia, microarray, oligonucleotide, FISH, cytogenetics, chromosome aberration

Background (dim); and chromosomal abnormalities detected by Chronic lymphocytic leukemia (CLL), the most common  fluorescence in situ hybridization (FISH) probes and leukemia diagnosed in adults from Western countries, is karyotyping. Conventional cytogenetics with karyotyping characterized by a monoclonal population of mature requires the use of an immunostimulatory CpG-oligodi- activated B lymphocytes that usually express CD5+ and nucleotide DSP 30 plus IL-2 cocktail to enhance the CD23+. However, the clinical features, disease course, yield of detectable chromosome aberrations in CLL and outcomes are highly variable. Most patients diag- cells. This cell culturing process is costly, time consum- nosed with CLL can survive for many years, but in a  ing, and requires the clinical indication of CLL at sam- subset of patients the course progresses more rapidly ple submission. Alternatively, FISH has been used to and is fatal despite aggressive treatment. detect specific prognostic chromosome markers in CLL Currently, the diagnosis of CLL is made using histo- using a panel of five to six probes. However, locus-spe- pathology; flow cytometry wi th a typical pattern of co- cific FISH does not reveal the complete cytogenetic pic- expression of CD5, CD23, CD20(dim), and surface Ig ture [1]. Prognostic markers, determined primarily using FISH, include deletions of 13q, 17p, and 11q and tris- * Correspondence: [e-mail] omy 12. Most anomalies detected by cytogenetics in 2 Signature Genomic Laboratories, PerkinElmer Inc., 2820 North Astor Street, CLL are copy number gains and losses; translocations S Fu p ll ok li a st ne o , f W au A t , h 9 o 9 r 2 i 0 n 7 f , or U m S a A tionisavailableattheendofthearticle are rarely identified [2]. © 2011 Kolquist et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.