Abstract

This work describes the identification and impact of somatic genomic abnormalities in human chronic lymphocytic leukemia (CLL). Using molecular cytogenetics (FISH) and G-banding cytogenetic analysis, chromosome abnormalities were detected in 37 of 46 (80.4%) CLL patients. 13q14 deletion was the most common finding followed by trisomy 12 and 11q22.3 deletion. 17p13 deletion was also detected as were several less frequent chromosome abnormalities. The presence of these abnormalities significantly influenced the period of treatment-free survival as well as other clinical characteristics. In particular, CLL samples with trisomy 12 and 11q22.3 deletion were associated with shorter treatment-free survival. In order to identify the under-lying molecular differences among CLL subgroups with different chromosome abnormalities, gene expression profiling was performed on a custom DNA microarray consisting of 10,000 human gene-specific oligonucleotides. A gene dosage effect was observed where the expression of genes at the genetic loci of the sites of the somatic genomic abnormality was altered in a fashion according to the type of genomic change. This phenomenon was particularly evident in CLL samples with trisomy 12 and 17p13 deletion. Thus, this study demonstrates that genomic abnormalities influence gene expression in CLL by a dosage effect.

Original languageEnglish (US)
Pages (from-to)769-778
Number of pages10
JournalInternational Journal of Molecular Medicine
Volume17
Issue number5
StatePublished - May 1 2006

Fingerprint

Gene Dosage
B-Cell Chronic Lymphocytic Leukemia
Gene Expression
Trisomy
Chromosome Aberrations
Genetic Loci
Survival
Cytogenetic Analysis
Gene Expression Profiling
Oligonucleotide Array Sequence Analysis
Oligonucleotides
Cytogenetics
Therapeutics
Genes

Keywords

  • Chronic lymphocytic leukemia
  • Genomic abnormalities

ASJC Scopus subject areas

  • Genetics

Cite this

@article{a4875501c1a6430494e2cc648a323046,
title = "Genomic abnormalities in chronic lymphocytic leukemia influence gene expression by a gene dosage effect",
abstract = "This work describes the identification and impact of somatic genomic abnormalities in human chronic lymphocytic leukemia (CLL). Using molecular cytogenetics (FISH) and G-banding cytogenetic analysis, chromosome abnormalities were detected in 37 of 46 (80.4{\%}) CLL patients. 13q14 deletion was the most common finding followed by trisomy 12 and 11q22.3 deletion. 17p13 deletion was also detected as were several less frequent chromosome abnormalities. The presence of these abnormalities significantly influenced the period of treatment-free survival as well as other clinical characteristics. In particular, CLL samples with trisomy 12 and 11q22.3 deletion were associated with shorter treatment-free survival. In order to identify the under-lying molecular differences among CLL subgroups with different chromosome abnormalities, gene expression profiling was performed on a custom DNA microarray consisting of 10,000 human gene-specific oligonucleotides. A gene dosage effect was observed where the expression of genes at the genetic loci of the sites of the somatic genomic abnormality was altered in a fashion according to the type of genomic change. This phenomenon was particularly evident in CLL samples with trisomy 12 and 17p13 deletion. Thus, this study demonstrates that genomic abnormalities influence gene expression in CLL by a dosage effect.",
keywords = "Chronic lymphocytic leukemia, Genomic abnormalities",
author = "Dickinson, {John D} and Avadhut Joshi and Javeed Iqbal and Warren Sanger and Bierman, {Philip Jay} and Joshi, {Shantaram S}",
year = "2006",
month = "5",
day = "1",
language = "English (US)",
volume = "17",
pages = "769--778",
journal = "International Journal of Molecular Medicine",
issn = "1107-3756",
publisher = "Spandidos Publications",
number = "5",

}

TY - JOUR

T1 - Genomic abnormalities in chronic lymphocytic leukemia influence gene expression by a gene dosage effect

AU - Dickinson, John D

AU - Joshi, Avadhut

AU - Iqbal, Javeed

AU - Sanger, Warren

AU - Bierman, Philip Jay

AU - Joshi, Shantaram S

PY - 2006/5/1

Y1 - 2006/5/1

N2 - This work describes the identification and impact of somatic genomic abnormalities in human chronic lymphocytic leukemia (CLL). Using molecular cytogenetics (FISH) and G-banding cytogenetic analysis, chromosome abnormalities were detected in 37 of 46 (80.4%) CLL patients. 13q14 deletion was the most common finding followed by trisomy 12 and 11q22.3 deletion. 17p13 deletion was also detected as were several less frequent chromosome abnormalities. The presence of these abnormalities significantly influenced the period of treatment-free survival as well as other clinical characteristics. In particular, CLL samples with trisomy 12 and 11q22.3 deletion were associated with shorter treatment-free survival. In order to identify the under-lying molecular differences among CLL subgroups with different chromosome abnormalities, gene expression profiling was performed on a custom DNA microarray consisting of 10,000 human gene-specific oligonucleotides. A gene dosage effect was observed where the expression of genes at the genetic loci of the sites of the somatic genomic abnormality was altered in a fashion according to the type of genomic change. This phenomenon was particularly evident in CLL samples with trisomy 12 and 17p13 deletion. Thus, this study demonstrates that genomic abnormalities influence gene expression in CLL by a dosage effect.

AB - This work describes the identification and impact of somatic genomic abnormalities in human chronic lymphocytic leukemia (CLL). Using molecular cytogenetics (FISH) and G-banding cytogenetic analysis, chromosome abnormalities were detected in 37 of 46 (80.4%) CLL patients. 13q14 deletion was the most common finding followed by trisomy 12 and 11q22.3 deletion. 17p13 deletion was also detected as were several less frequent chromosome abnormalities. The presence of these abnormalities significantly influenced the period of treatment-free survival as well as other clinical characteristics. In particular, CLL samples with trisomy 12 and 11q22.3 deletion were associated with shorter treatment-free survival. In order to identify the under-lying molecular differences among CLL subgroups with different chromosome abnormalities, gene expression profiling was performed on a custom DNA microarray consisting of 10,000 human gene-specific oligonucleotides. A gene dosage effect was observed where the expression of genes at the genetic loci of the sites of the somatic genomic abnormality was altered in a fashion according to the type of genomic change. This phenomenon was particularly evident in CLL samples with trisomy 12 and 17p13 deletion. Thus, this study demonstrates that genomic abnormalities influence gene expression in CLL by a dosage effect.

KW - Chronic lymphocytic leukemia

KW - Genomic abnormalities

UR - http://www.scopus.com/inward/record.url?scp=33750604336&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750604336&partnerID=8YFLogxK

M3 - Article

VL - 17

SP - 769

EP - 778

JO - International Journal of Molecular Medicine

JF - International Journal of Molecular Medicine

SN - 1107-3756

IS - 5

ER -