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Series GSE143385

Query DataSets for GSE143385

Status

Public on Sep 25, 2020

Title

microRNA expression analysis of metastatic adrenocortical tumors

Organism

Homo sapiens

Experiment type

Non-coding RNA profiling by array

Summary

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.

Overall design

Tumor samples embedded in OCT were sectioned, stained with hematoxylin and eosin and reviewed by a pathologist. RNA was extracted from 50-100 mg of tumor using the Qiagen miRNeasy Kit and then used for microRNA pofiling. Author states 'I have no raw data'. Thus, this submissionis incomplete.

Contributor(s)

Litman T, Bates SE, Fojo AT

Citation(s)

33148256

Submission date

Jan 09, 2020

Last update date

Nov 09, 2020

Contact name

Thomas Litman

E-mail(s)

tlitman@hotmail.com