Genetic landscape of pediatric Adrenocortical Tumor
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ABSTRACT:
PROVIDER: EGAS00001000257 | EGA |
REPOSITORIES: EGA
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Project description:Pediatric adrenocortical carcinomas (ACCs) are aggressive; the overall survival of pediatric patients with ACCs is 40%-50%. Appropriate staging and histologic classification are crucial as children with incompletely resected tumors or metastatic disease have a dismal prognosis. The clinical course of pediatric adrenocortical tumors (ACTs) is difficult to predict using the current classification schemas, which rely heavily on subjective microscopic and gross macroscopic variables. Recent advances in adult ACT studies have revealed distinct DNA-methylation patterns with prognostic significance that have not been systematically interrogated in the pediatric population.
2020-05-16 | GSE131350 | GEO
Project description:SF-1, a transcription factor belonging to the nuclear receptor superfamily, has a pivotal role for adrenogonadal development in humans and mice. A constant feature of childhood adrenocortical tumors (ACT) is SF-1 amplification and overexpression. Using an inducible cellular system, here we show that SF-1 overexpression increases human adrenocortical cell proliferation through opposing effects on cell cycle and apoptosis. SF-1 overexpression also selectively modulates steroidogenesis, reducing cortisol and aldosterone secretion. We identified a novel pro-apoptotic factor for adrenocortical cells, NOV/CCN3, whose levels are significantly reduced by SF-1 overexpression in human adrenocortical cells and are also reduced in primary adrenal tumors. Moreover, Sf-1 overexpression triggers adrenocortical hyperplasia and tumor formation in mice. These tumors express gonadal markers and activated Stat3. Our studies reveal the critical role of SF-1 gene dosage for adrenocortical tumorigenesis and constitute a rationale for the development of drugs targeting SF-1 transcriptional activity for ACT therapy. Keywords: differential expression, transcription factor
2007-01-01 | GSE5911 | GEO
Project description:SNP array data from 13 Brazilian childhood adrenocortical tumors (ACTs) were analyzed to detect recurrent copy number changes and highlight potential candidate driver genes. 13 childhood ACT were analyzed with Illumina HumanCNV370-Duo v1.0 chips. Paired normal blood samples from 6 patients were analyzed with Illumina HumanCNV370-Quad v3.0 chips.
2012-03-23 | E-GEOD-24804 | biostudies-arrayexpress
Project description:Pediatric adrenocortical tumors (ACT) are rare and often fatal malignancies; little is known regarding their etiology and biology. To provide additional insight into the nature of ACT, we determined the gene expression profiles of 24 pediatric tumors (five adenomas, 18 carcinomas, and one undetermined) and seven normal adrenal glands. Distinct patterns of gene expression, validated by quantitative real-time PCR and Western blot analysis, were identified that distinguish normal adrenal cortex from tumor. Differences in gene expression were also identified between adrenocortical adenomas and carcinomas. In addition, pediatric adrenocortical carcinomas were found to share similar patterns of gene expression when compared with those published for adult ACT. This study represents the first microarray analysis of childhood ACT. Our findings lay the groundwork for establishing gene expression profiles that may aid in the diagnosis and prognosis of pediatric ACT, and in the identification of signaling pathways that contribute to this disease.
2015-11-25 | GSE75415 | GEO
Project description:SF-1, a transcription factor belonging to the nuclear receptor superfamily, has a pivotal role for adrenogonadal development in humans and mice. A constant feature of childhood adrenocortical tumors (ACT) is SF-1 amplification and overexpression. Using an inducible cellular system, here we show that SF-1 overexpression increases human adrenocortical cell proliferation through opposing effects on cell cycle and apoptosis. SF-1 overexpression also selectively modulates steroidogenesis, reducing cortisol and aldosterone secretion. We identified a novel pro-apoptotic factor for adrenocortical cells, NOV/CCN3, whose levels are significantly reduced by SF-1 overexpression in human adrenocortical cells and are also reduced in primary adrenal tumors. Moreover, Sf-1 overexpression triggers adrenocortical hyperplasia and tumor formation in mice. These tumors express gonadal markers and activated Stat3. Our studies reveal the critical role of SF-1 gene dosage for adrenocortical tumorigenesis and constitute a rationale for the development of drugs targeting SF-1 transcriptional activity for ACT therapy. Keywords: differential expression, transcription factor Gene expression profiles were analyzed in two different H295R TR/SF-1 WT clones overexpressing SF-1 in a tetracycline-regulated fashion cultured in basal conditions or after three days of doxycycline treatment. For each condition, two biological replicates were examined. Array #22354 Clone #1 replicate 1 basal Cy3/Dox Cy5 Array #22416 Clone #1 replicate 2 basal Cy5/Dox Cy3 Array #22446 Clone #2 replicate 1 basal Cy3/Dox Cy5 Array #22447 Clone #2 replicate 2 basal Cy5/Dox Cy3
2010-06-11 | E-GEOD-5911 | biostudies-arrayexpress
Project description:Purpose: The management of adrenocortical tumors (ACTs) is complex, compounded by the difficulty in discriminating benign from malignant tumors using conventional histology. The Weiss score is the current most widely used system for ACT diagnosis but it has limitations, particularly with ACTs with a score of 3. The am of this study was to identify molecular markers whose expression can discriminate adrenocortical carcinomas (ACCs) from adrenocortical adenomas (ACAs) by microarray gene expression profiling and to determine their clinical applicability by using immunohistochemistry (IHC). Experimental design: Microarray gene expression profiling was used to identify 7 molecular markers which were significantly differentially expressed between ACCs and ACAs. These results were confirmed with quantitative PCR for all 7 genes and IHC for 3 protein. Results: Microarray gene expression profiling was able to accurately categorize ACTs into ACCs and ACAs. All 7 genes were strong discriminators of ACCs from ACAs on qPCR. IHC with IGF2, MAD2L1, CCNB1 and Ki-67, but not ACADVL or ALOX15B, had high diagnostic accuracy in differentiating ACCs from ACAs. The best results however were obtained with a combination of IGF2 and Ki-67 with 96% sensitivity and 100% specificity in diagnosing ACCs. Conclusion: Microarray gene expression profiling accurately differentiates ACCs from ACAs. The combination of IGF2 and Ki-67 IHC is also highly accurate in distinguishing between the 2 groups and is particularly helpful in ACTs with Weiss score of 3. Keywords: Adrenocortical carcinoma, adrenocortical adenoma, differential gene expression, immunohistochemistry, qPCR
2009-07-29 | GSE12368 | GEO
Project description:Pediatric adrenocortical tumors (ACT) are rare and often fatal malignancies; little is known regarding their etiology and biology. To provide additional insight into the nature of ACT, we determined the gene expression profiles of 24 pediatric tumors (five adenomas, 18 carcinomas, and one undetermined) and seven normal adrenal glands. Distinct patterns of gene expression, validated by quantitative real-time PCR and Western blot analysis, were identified that distinguish normal adrenal cortex from tumor. Differences in gene expression were also identified between adrenocortical adenomas and carcinomas. In addition, pediatric adrenocortical carcinomas were found to share similar patterns of gene expression when compared with those published for adult ACT. This study represents the first microarray analysis of childhood ACT. Our findings lay the groundwork for establishing gene expression profiles that may aid in the diagnosis and prognosis of pediatric ACT, and in the identification of signaling pathways that contribute to this disease. We used microarrays to explore the expression profiles differentially expressed in childhood adrenocortical tumors and in normal adrenal gland tissues. Pediatric adrenocortical adenoma and carcinoma patients were enrolled on the International Pediatric Adrenocortical Tumor Registry (IPACTR) and Bank protocol. Tumor specimens were harvested during surgery and snap frozen in liquid nitrogen to preserve tissue integrity. Data have been compiled for eight males and 15 females between 0 and 16 years of age. Table 1 (West et al, Cancer Research 67:601-608, 2007) summarizes the primary clinical information for each subject (excluding sample Unk1 with ACT of undetermined histology), including stage of the disease, tumor class, sex, age, relapse-free survival, and overall survival.
2015-11-25 | E-GEOD-75415 | biostudies-arrayexpress
Project description:We studied the miRNA expression profile of a series of childhood adrenocortical tumors (ACT) and age-matched normal adrenal samples
2010-04-01 | GSE19856 | GEO
Project description:We studied the miRNA expression profile of a series of childhood adrenocortical tumors (ACT) and age-matched normal adrenal samples 25 ACT - 5 normal
2010-04-01 | E-GEOD-19856 | biostudies-arrayexpress
Project description:SNP array data from 12 childhood adrenocortical tumors (ACT) were used to identify recurrent chromosome rearrangements and candidate driver genes.
2012-04-02 | GSE35064 | GEO