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Integrated Genomic Profiling Identifies Loss of Chromosome 11p Impacting Transcriptomic Activity in Aggressive Pituitary PRL Tumors
Author(s) -
Wierinckx Anne,
Roche Magali,
Raverot Gérald,
LegrasLachuer Catherine,
Croze Séverine,
Nazaret Nicolas,
Rey Catherine,
Auger Carole,
Jouanneau Emmanuel,
Chanson Philippe,
Trouillas Jacqueline,
Lachuer Joël
Publication year - 2011
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2011.00476.x
Subject(s) - transcriptome , computational biology , pituitary tumors , profiling (computer programming) , biology , cancer research , genetics , bioinformatics , gene , computer science , endocrinology , gene expression , operating system
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.

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