Identification of a novel recurrent gain on 20q13 in chronic lymphocytic leukemia by array CGH and gene expression profiling.
BACKGROUND
The presence of genetic changes is a hallmark of chronic lymphocytic leukemia (CLL). The most common cytogenetic abnormalities with independent prognostic significance in CLL are 13q14, ATM and TP53 deletions and trisomy 12. However, CLL displays a great genetic and biological heterogeneity. The aim of this study was to analyze the genomic imbalances in CLL cytogenetic subsets from both genomic and gene expression perspectives to identify new recurrent alterations.


METHODS
The genomic imbalances and expression levels of 67 patients were analyzed. The novel recurrent abnormalities detected with bacterial artificial chromosome array were confirmed by FISH and oligonucleotide microarrays. In all cases, gene expression profiling was assessed.


RESULTS
Copy number alterations were identified in 75% of cases. Overall, the results confirmed FISH studies for the regions frequently involved in CLL and also defined a new recurrent gain on chromosome 20q13.12, in 19% (13/67) of the CLL patients. Oligonucleotide expression correlated with the regions of loss or gain of genomic material, suggesting that the changes in gene expression are related to alterations in copy number.


CONCLUSIONS
Our study demonstrates the presence of a recurrent gain in 20q13.12 associated with overexpression of the genes located in this region, in CLL cytogenetic subgroups.
IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca-CSIC, Salamanca.
A E
AE
Rodríguez
IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca-CSIC, Salamanca.
C
C
Robledo
Instituto de Estudios de Ciencias de la Salud de Castilla y León (IECSCYL)-HUSAL, Castill y León.
J L
JL
García
Department of Hematology, Hospital Clínico Universitario de Salamanca, Salamanca.
M
M
González
Department of Hematology, Hospital Clínico Universitario de Salamanca, Salamanca.
N C
NC
Gutiérrez
Department of Hematology, Hospital Infanta Leonor, Madrid.
J A
JA
Hernández
Department of Hematology, Hospital Virgen Blanca, León.
V
V
Sandoval
Department of Hematology, Hospital Clínico Universitario, Valladolid.
A
A
García de Coca
Department of Hematology, Hospital Nuestra Señora de Sonsoles, Ávila.
I
I
Recio
Bioinformatics and Functional Genomics, Centro de Investigación del Cáncer, Universidad de Salamanca-CSIC, Salamanca.
A
A
Risueño
Department of Hematology, Hospital Virgen del Puerto, Plasencia.
G
G
Martín-Núñez
Genomics and Proteomics Unit, Centro de Investigación del Cáncer, Universidad de Salamanca-CSIC, Salamanca.
E
E
García
Department of Hematology, Hospital General de Segovia, Segovia.
R
R
Fisac
Department of Hematology, Hospital del Río Hortega, Valladolid, Spain.
J
J
Conde
Bioinformatics and Functional Genomics, Centro de Investigación del Cáncer, Universidad de Salamanca-CSIC, Salamanca.
J
J
de Las Rivas
IBMCC, Centro de Investigación del Cáncer, Universidad de Salamanca-CSIC, Salamanca; Department of Hematology, Hospital Clínico Universitario de Salamanca, Salamanca. Electronic address: jmhr@usal.es.
J M
JM
Hernández
D002869:Chromosome Aberrations; D002890:Chromosomes, Human, Pair 20; D055028:Comparative Genomic Hybridization; D018628:Gene Dosage; D020869:Gene Expression Profiling; D042822:Genomic Instability; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000235:genetics*