Integrated genomic profiling identifies loss of chromosome 11p impacting transcriptomic activity in aggressive
Anne Wierinckx1, Magali Roche, Gérald Raverot
1INSERM, U842, Lyon, France.
Abstract:
Integrative genomics approaches associating DNA structure and transcriptomic analysis should allow the identification of cascades of events relating to tumor aggressiveness. While different genome alterations have been identified in pituitary tumors, none have ever been correlated with the aggressiveness. This study focused on one subtype of pituitary tumor, the prolactin (PRL) pituitary tumors, to identify molecular events associated with the aggressive and malignant phenotypes. We combined a comparative genomic hybridization and transcriptomic analysis of 13 PRL tumors classified as nonaggressive or aggressive. Allelic loss within the p arm region of chromosome 11 was detected in five of the aggressive tumors. Allelic loss in the 11q arm was observed in three of these five tumors, all three of which were considered as malignant based on the occurrence of metastases. Comparison of genomic and transcriptomic data showed that allelic loss impacted upon the expression of genes located in the imbalanced region. Data filtering allowed us to highlight five deregulated genes (DGKZ, CD44, TSG101, GTF2H1, HTATIP2), within the missing 11p region, potentially responsible for triggering the aggressive and malignant phenotypes of PRL tumors. Our combined genomic and transcriptomic analysis underlines the importance of chromosome allelic loss in determining the aggressiveness and malignancy of tumors.
Insights
Genomic analysis of prolactin (PRL) pituitary tumors reveals that chromosome 11 allelic loss is linked to tumor aggressiveness and malignancy. This finding identifies key genes potentially driving aggressive tumor phenotypes.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Pituitary tumors are common, but molecular drivers of aggressiveness remain poorly understood.
- Previous genomic studies have identified alterations in pituitary tumors but not linked them to tumor behavior.
- Prolactin (PRL) pituitary tumors are a significant subtype requiring investigation into their aggressive potential.
Purpose of the Study:
- To identify molecular events associated with aggressive and malignant phenotypes in prolactin (PRL) pituitary tumors.
- To correlate genomic alterations with transcriptomic changes in PRL tumors.
- To pinpoint specific genes involved in PRL tumor aggressiveness.
Main Methods:
- Comparative genomic hybridization (CGH) and transcriptomic analysis were performed on 13 PRL tumors.
- Tumors were classified as nonaggressive or aggressive based on clinical and pathological features.
- Genomic data was integrated with transcriptomic data to identify deregulated genes in imbalanced chromosomal regions.
Main Results:
- Allelic loss in the 11p chromosomal region was detected in aggressive PRL tumors.
- Allelic loss in the 11q arm was associated with malignant PRL tumors exhibiting metastases.
- Five deregulated genes (DGKZ, CD44, TSG101, GTF2H1, HTATIP2) in the 11p region were identified as potentially responsible for tumor aggressiveness.
Conclusions:
- Combined genomic and transcriptomic analysis is crucial for understanding tumor aggressiveness.
- Chromosome allelic loss, particularly in the 11p region, plays a significant role in the aggressiveness and malignancy of PRL pituitary tumors.
- The identified deregulated genes represent potential therapeutic targets for aggressive PRL tumors.
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