Related Experiment Video
Updated: Jul 4, 2026
Array Comparative Genomic Hybridization (Array CGH) for Detection of Genomic Copy Number Variants
Published on: February 21, 2015
DNA copy number changes in high-grade malignant peripheral nerve sheath tumors by array CGH
Stine H Kresse1, Magne Skårn, Hege O Ohnstad
1Department of Tumor Biology, Radiumhospitalet, Rikshospitalet, Oslo, Norway. stinek@rr-research.no
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.
Insights
This study analyzed DNA copy number changes in malignant peripheral nerve sheath tumors (MPNSTs) to identify new gene targets. Gains in the 17q region correlated with poor prognosis, highlighting TOP2A, ETV4, and BIRC5 as potential therapeutic targets.
Area of Science:
- Genomics
- Oncology
- Molecular Biology
Background:
- Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue tumors with complex chromosomal abnormalities.
- Understanding genetic alterations is crucial for identifying MPNST development and progression targets.
Purpose of the Study:
- To identify recurrent chromosomal regions of gain and loss in MPNSTs.
- To discover novel gene targets associated with MPNST development and progression.
Main Methods:
- Utilized microarray-based comparative genomic hybridization (array CGH) to analyze DNA copy number changes in seven high-grade MPNSTs.
- Employed cDNA microarray and quantitative real-time reverse transcription PCR to assess gene expression within identified chromosomal regions.
Main Results:
- Frequent gains were observed, particularly in regions 1q24.1-q24.2, 1q24.3-q25.1, 8p23.1-p12, 9q34.11-q34.13, and 17q23.2-q25.3.
- The 17q23.2-q25.3 region gain correlated with poor patient outcomes.
- Genes TOP2A, ETV4, and BIRC5 within the 17q region showed increased expression and are potential targets for the 17q gain associated with poor survival.
Conclusions:
- DNA copy number changes detected by array CGH can predict MPNST patient prognosis.
- TOP2A, ETV4, and BIRC5 are identified as promising candidate targets for the 17q gain linked to poor survival in MPNSTs.
More Related Videos
08:57Identifying, Diagnosing, and Grading Malignant Peripheral Nerve Sheath Tumors in Genetically Engineered Mouse Models
Published on: May 17, 2024
09:33Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor
Published on: August 25, 2023
Related Concept Videos
02:26Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
01:17Karyotyping