Dataset Information

Detection of clinically relevant exonic copy-number changes by array CGH.

ABSTRACT: Array comparative genomic hybridization (aCGH) is a powerful tool for the molecular elucidation and diagnosis of disorders resulting from genomic copy-number variation (CNV). However, intragenic deletions or duplications--those including genomic intervals of a size smaller than a gene--have remained beyond the detection limit of most clinical aCGH analyses. Increasing array probe number improves genomic resolution, although higher cost may limit implementation, and enhanced detection of benign CNV can confound clinical interpretation. We designed an array with exonic coverage of selected disease and candidate genes and used it clinically to identify losses or gains throughout the genome involving at least one exon and as small as several hundred base pairs in size. In some patients, the detected copy-number change occurs within a gene known to be causative of the observed clinical phenotype, demonstrating the ability of this array to detect clinically relevant CNVs with subkilobase resolution. In summary, we demonstrate the utility of a custom-designed, exon-targeted oligonucleotide array to detect intragenic copy-number changes in patients with various clinical phenotypes.

SUBMITTER: Boone PM

PROVIDER: S-EPMC3158569 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Detection of clinically relevant exonic copy-number changes by array CGH.

Boone Philip M PM Bacino Carlos A CA Shaw Chad A CA Eng Patricia A PA Hixson Patricia M PM Pursley Amber N AN Kang Sung-Hae L SH Yang Yaping Y Wiszniewska Joanna J Nowakowska Beata A BA del Gaudio Daniela D Xia Zhilian Z Simpson-Patel Gayle G Immken LaDonna L LL Gibson James B JB Tsai Anne C-H AC Bowers Jennifer A JA Reimschisel Tyler E TE Schaaf Christian P CP Potocki Lorraine L Scaglia Fernando F Gambin Tomasz T Sykulski Maciej M Bartnik Magdalena M Derwinska Katarzyna K Wisniowiecka-Kowalnik Barbara B Lalani Seema R SR Probst Frank J FJ Bi Weimin W Beaudet Arthur L AL Patel Ankita A Lupski James R JR Cheung Sau Wai SW Stankiewicz Pawel P

Human mutation 20101102 12

Array comparative genomic hybridization (aCGH) is a powerful tool for the molecular elucidation and diagnosis of disorders resulting from genomic copy-number variation (CNV). However, intragenic deletions or duplications--those including genomic intervals of a size smaller than a gene--have remained beyond the detection limit of most clinical aCGH analyses. Increasing array probe number improves genomic resolution, although higher cost may limit implementation, and enhanced detection of benign C ...[more]

PMID: 20848651

Similar Datasets

Project description:BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare and highly aggressive soft tissue tumors showing complex chromosomal aberrations. In order to identify recurrent chromosomal regions of gain and loss, and thereby novel gene targets of potential importance for MPNST development and/or progression, we have analyzed DNA copy number changes in seven high-grade MPNSTs using microarray-based comparative genomic hybridization (array CGH). RESULTS: Considerable more gains than losses were observed, and the most frequent minimal recurrent regions of gain included 1q24.1-q24.2, 1q24.3-q25.1, 8p23.1-p12, 9q34.11-q34.13 and 17q23.2-q25.3, all gained in five of seven samples. The 17q23.2-q25.3 region was gained in all five patients with poor outcome and not in the two patients with disease-free survival. cDNA microarray analysis and quantitative real-time reverse transcription PCR were used to investigate expression of genes located within these regions. The gene lysyl oxidase-like 2 (LOXL2) was identified as a candidate target for the 8p23.1-p12 gain. Within 17q, the genes topoisomerase II-alpha (TOP2A), ets variant gene 4 (E1A enhancer binding protein, E1AF) (ETV4) and baculoviral IAP repeat-containing 5 (survivin) (BIRC5) showed increased expression in all samples compared to two benign tumors. Increased expression of these genes has previously been associated with poor survival in other malignancies, and for TOP2A, in MPNSTs as well. In addition, we have analyzed the expression of five micro RNAs located within the 17q23.2-q25.3 region, but none of them showed high expression levels compared to the benign tumors. CONCLUSION: Our study shows the potential of using DNA copy number changes obtained by array CGH to predict the prognosis of MPNST patients. Although no clear correlations between the expression level and patient outcome were observed, the genes TOP2A, ETV4 and BIRC5 are interesting candidate targets for the 17q gain associated with poor survival.

Dataset Information

Detection of clinically relevant exonic copy-number changes by array CGH.

Publications

Detection of clinically relevant exonic copy-number changes by array CGH.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets