Genomic alterations of chromosome 11 induce transcriptomic dysregulation in aggressive and malignant prolactin tumours

ABSTRACT: Pituitary tumors are generally considered as benign. However, many are invasive (45 to 55%) and some are described as aggressive with a high proliferation rate and short post-operative time to recurrence and 0.2% metastasize. The molecular events associated to the progression of the pituitary tumor toward an aggressive and malignant phenotype is still unresolved. To bring new hypothesis on signaling pathways associated to the tumor progression, we applied a wide genome analysis approach combining transcriptome analysis and CGH analysis on the same 13 prolactin tumours classified as non-invasive (n=5), invasive (n=2) and agressive-invasive tumors (n=6). In 5/6 agressive-invasive tumours a loss of a common region in the p arm of the chromosome 11 was detected. This region extending from position 14.9 to position 46.5 Mb harbours the cytobands 11p15.2, 11p15.1, 11p14.3, 11p14.2, 11p14.1, 11p13, 11p12 and 11p11.2. In 3 of these 5 tumours considered as carcinomas because of the presence of metastasis, an allelic loss is also observed in the 11q arm. The combination of data coming from genome structure exploration and transcriptomic analysis showed that allelic loss impact the expression of genes harbored in the imbalanced region. Data filtering strategy allowed us to highlight among the 139 genes harbored in the 11p region loss, 5 genes (DGKZ, CD44, TSG101, GTF2H1 and HTATIP2) that could be candidate gene for triggering the progression of prolactin tumour toward an aggressive and malignant phenotype. Finally, specific DNA alterations give one molecular argument more to consider agressive-invasive tumour and carcinomas as a distinct step in progression of the pituitary tumours. Copy number analysis of Affymetrix Genome-Wide Human SNP Array 6.0 was performed for 13 prolactin tumors, 6 aggressive-invasive, 2 invasive, 5 non-invasive. The same analysis was performed for one normal pituitary and one genomic DNA called "reference 103" from Affymetrix.

ORGANISM(S): Homo sapiens

SUBMITTER: Joël LACHUER 

PROVIDER: E-GEOD-22615 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress