Genomic alterations of chromosome 11 induce transcriptome dysregulation in aggressive and malignant prolactin tumours
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Joël LACHUER
PROVIDER: E-GEOD-32191 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Integrated genomic profiling identifies loss of chromosome 11p impacting transcriptomic activity in aggressive pituitary PRL tumors.
Wierinckx Anne A Roche Magali M Raverot Gérald G Legras-Lachuer Catherine C Croze Séverine S Nazaret Nicolas N Rey Catherine C Auger Carole C Jouanneau Emmanuel E Chanson Philippe P Trouillas Jacqueline J Lachuer Joël J
Brain pathology (Zurich, Switzerland) 20110223 5
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 c ...[more]
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When two follicles were ≥ 17mm, human chorionic gonadotropin (hCG) (10,000 IU; Novarel®) was administered. Oocytes were retrieved 35 h post-hCG. Following oocyte recovery, GC were immediately collected in RNALater®. Pooled GC from individual patients were washed, centrifuged over 40% Percoll®, resuspended in RNALater, and snap-frozen in LN. Total RNA was extracted and stored at -70C. Biotinylated cRNA was synthesized from total RNA and each sample was run individually on CodeLink Whole Human Genome Bioarrays (Applied Microarrays Quality control steps: The cRNA that was synthesized from the granulosa cells from individual patients was used for hybridization to a single CodeLink (Applied Microarrays) Whole Human Genome microarray. Only one sample was hybridized with each slide and only one dye (Alexa 647) was used so no dye swaps were necessary. Bacterial control spikes were used as per manufacturer's instructions. Samples used, extract preparation and labelling: The origin of each biological sample: Granulosa cells from women < 35 years-old undergoing in vitro fertilization. Manipulations of biological samples and protocols used: Female patients were treated with gonadotropin releasing hormone (GnRH) agonist long protocol plus individualized dosages of (1) recombinant follicle stimulating hormone (rFSH) (Gonal-F®) (n=4) or (2) purified human menopausal gonadotropin (hMG; Menopur®; 75 IU FSH/75 IU LH per vial) (n=3). Follicle development was monitored by ultrasound and serum estradiol levels. When two follicles were ≥ 17mm, human chorionic gonadotropin (hCG) (10,000 IU; Novarel®) was administered. Oocytes were retrieved 35 h post-hCG. Following oocyte recovery, granulosa cells were immediately collected in RNALater®. Pooled GC from individual patients were washed, centrifuged over 40% Percoll®, resuspended in RNALater, and snap-frozen in LN. Experimental factor: treatment with recombinant FSH versus purified human menopausal gonadotropin Technical protocols: Granulosa cells were collected into RNAlater (Ambion) and stored at -80C until processed. The granulosa cells were pelleted by centrifugation to remove the RNAlater. Each cell pellet was homogenized in TRI reagent (Molecular Research Centers). Bromochloropropane and sodium acetate were added, and the samples were centrifuged to separate the phases. The RNA-containing layer was removed and the RNA purified on an RNeasy extraction column (Qiagen). The sample was treated with an on-column DNase treatment (RNase-free DNase, Qiagen). The purity and quantity were evaluated by an Agilent Bioanalyzer using the RNA 6000 Nanoassay LabChip. Labelled cRNA was prepared using the manufacturer's Instruction Protocol (www1.amershambiosciences.com, CodeLink Gene Expression System: Manual Labelled cRNA Target Preparation). The source of reagents was the CodeLink Expression Assay Reagent Kit, Manual Prep, except where specified otherwise. 0.285 micrograms of total granulosa cell RNA was mixed with bacterial control RNA spikes and primed with T7 oligo(dT) primer for 10 min at 70C. (The bacterial control spikes included araB, entF, fixB, gnd, hisB, and leuB.) The first strand of cDNA was synthesized with first strand buffer, dNTP mix, RNase inhibitor, and reverse transcriptase for 2 h at 42C. The second strand cDNA synthesis reaction was prepared using second strand buffer, dNTP mix, DNA polymerase mix, and RNase H; the reaction was carried out for 2h at 16C. The double-stranded cDNA was purified on QIAquick columns (Qiagen) and the eluent was dried down in a SpeedVac concentrator. The double-stranded cDNA was resuspended in a mixture containing T7 reaction buffer, T7 ATP, T7 GTP, T7 UTP, T7 CTP, biotin-11-UTP, and T7 enzyme mix for the synthesis of cRNA. 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2010-03-22 | E-GEOD-16523 | biostudies-arrayexpress