Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA484071 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors
| PRJNA484072 | ENA
Project description:Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and high mortality due to metastatic disease. All reported genetic alterations have been in primary ACC, and it is unknown if there is molecular heterogeneity in ACC. Here, we report the genetic changes associated with metastatic ACC compared to primary ACCs and tumor heterogeneity. We performed whole-exome sequencing of 33 metastatic tumors. The overall mutation rate (per megabase) in metastatic tumors was 2.8-fold higher than primary ACC tumor samples. We found tumor heterogeneity among different metastatic sites in ACC and discovered recurrent mutations in several novel genes. We observed 37-57% overlap in genes that are mutated among different metastatic sites within the same patient. We also identified new therapeutic targets in recurrent and metastatic ACC not previously described in primary ACCs.
| S-EPMC6178360 | biostudies-literature
Project description:CXCR4 expression by metastatic adrenocortical carcinoma is heterogeneous among patients and among lesions We used microarrays for 57 ACC metastases from 42 patients to evaluate gene expression in different lesions from same patients and over time, focusing on CXCR4 expression and other genes correlating with CXCR4 expression
2017-11-24 | GSE90713 | GEO
Project description:Background: Adrenocortical carcinoma (ACC) is a rare, often-aggressive neoplasm of the adrenal cortex, with a 14.5-month median overall survival. We asked whether tumors from patients with advanced or metastatic ACC would offer clues as to putative genes that might have critical roles in disease progression or in more aggressive disease biology. Methods: We conducted comprehensive genomic and expression analyses of 43 ACCs. Results: Copy number gains and losses matched that previously reported. We identified a median mutation rate of 3.38 per megabase (Mb), somewhat higher than in a previous study possibly related to the more advanced disease. The mutational signature was characterized by a predominance of C>T, C>A and T>C transitions. As in previously reports, only cancer genes TP53 (26%) and beta-catenin (CTNNB1, 14%) were mutated in more than 10% of samples. The TCGA-identified putative cancer genes MEN1 and PRKAR1A were found in low frequency – 4.7% and 2.3%, respectively. Most of the mutations were in genes not implicated in the etiology or maintenance of cancer. Specifically, amongst the 38 genes that were mutated in more than 9% of samples, only four were represented in Tier 1 of the 576 COSMIC Cancer Gene Census (CCGC). Thus, 82% of genes found to have mutations likely have no role in the etiology or biology of ACC; while the role of the other 18%, if any, remains to be proven. Finally, the transcript length for the 38 most frequently mutated genes in ACC is statistically longer than the average of all coding genes, raising the question of whether transcript length in part determined mutation probability. Conclusions: We conclude that the mutational and expression profiles of advanced and metastatic tumors is very similar to those from newly diagnosed patients –with very little in the way of genomic aberration to explain it. Our data and that in the previous analyses finds the rate of mutations in ACCs lower than that in other cancers and suggests an epigenetic basis for the disease should be the focus of future studies. The Affymetrix PrimeView platform was used for the gene expression profiling.
2020-09-25 | GSE143383 | GEO
Project description:Background: Adrenocortical carcinoma (ACC) is a rare, often-aggressive neoplasm of the adrenal cortex, with a 14.5-month median overall survival. We asked whether tumors from patients with advanced or metastatic ACC would offer clues as to putative genes that might have critical roles in disease progression or in more aggressive disease biology. Methods: We conducted comprehensive genomic and expression analyses, including microRNA profiling, of 33 ACCs and 6 normal adrenals. Results: Copy number gains and losses matched that previously reported. We identified a median mutation rate of 3.38 per megabase (Mb), somewhat higher than in a previous study possibly related to the more advanced disease. The mutational signature was characterized by a predominance of C>T, C>A and T>C transitions. As in previously reports, only cancer genes TP53 (26%) and beta-catenin (CTNNB1, 14%) were mutated in more than 10% of samples. The TCGA-identified putative cancer genes MEN1 and PRKAR1A were found in low frequency – 4.7% and 2.3%, respectively. Most of the mutations were in genes not implicated in the etiology or maintenance of cancer. Specifically, amongst the 38 genes that were mutated in more than 9% of samples, only four were represented in Tier 1 of the 576 COSMIC Cancer Gene Census (CCGC). Thus, 82% of genes found to have mutations likely have no role in the etiology or biology of ACC; while the role of the other 18%, if any, remains to be proven. Finally, the transcript length for the 38 most frequently mutated genes in ACC is statistically longer than the average of all coding genes, raising the question of whether transcript length in part determined mutation probability. Conclusions: We conclude that the mutational and expression profiles of advanced and metastatic tumors is very similar to those from newly diagnosed patients –with very little in the way of genomic aberration to explain it. Our data and that in the previous analyses finds the rate of mutations in ACCs lower than that in other cancers and suggests an epigenetic basis for the disease should be the focus of future studies. The Exiqon miRCURY LNA microRNA array v.11.0 platform was used for the microRNA profiling.
2020-09-25 | GSE143385 | GEO
Project description:Title: Elevated SGPL1 expression increases metabolic rate and reduces survival in adrenocortical carcinoma patients
| PRJNA786217 | ENA
Project description:microRNA expression analysis of metastatic adrenocortical tumors
| PRJNA600261 | ENA
Project description:Gene expression analysis of metastatic adrenocortical tumors
| PRJNA600262 | ENA
Project description:Estimation of the spontaneous mutation rate in Heliconius melpomene
| PRJEB7581 | ENA
Project description:Transcription factor 21 (TCF21) directly binds and regulates SF1 in tumor and normal adrenocortical cells, and both are involved in the development and steroidogenesis of the adrenal cortex. TCF21 is a tumor suppressor gene and its expression is reduced in malignant tumors. In adrenocortical tumors, it is less expressed in adrenocortical carcinomas (ACC) than in adrenocortical adenomas (ACA) and normal tissue. However, a comprehensive analysis to identify TCF21 targets have not yet been conducted in any type of cancer. In this study, we performed Chromatin Immunoprecipitation and Sequencing (ChIP-Seq) in adrenocortical carcinoma cell line (NCI-H295R) overexpressing TCF21, with the aim of identifying TCF21 new targets. The five most frequently identified sequences corresponded to the PRDM7, CNTNAP2, CACNA1B, PTPRN2 and KCNE1B genes. Validation experiments showed that, in NCI-H295R cells, TCF21 regulates gene expression positively in PRDM7 and negatively in CACNA1B. Recently, it was observed that the N-type calcium channel v2.2 (Cav2.2) encoded by CACNA1B gene is important in Angiotensin II signal transduction for corticosteroid biosynthesis in NCI-H295R adrenocortical carcinoma cells. Indeed, TCF21 inhibits CACNA1B and Cav2.2 expression in NCI-H295R. In addition, in a cohort of 55 adult patients with adrenocortical tumor, CACNA1B expression was higher in ACC than ACA, and was related to poor disease-free survival in ACC patients. These results suggest a mechanism of steroidogenesis control by TCF21 in adrenocortical tumor cells, in addition to the control observed through SF1 inhibition. Importantly, steroid production could impair tumor immunogenicity, contributing to the immune resistance described in adrenal cancer.
2022-06-30 | GSE179308 | GEO