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Tumor Heterogeneity in Metastatic Adrenocortical Tumors

ABSTRACT:

We have analyzed 33 human metastatic adrenocortical tumors from 14 patients with advanced metastases and performed whole exome sequencing to identify novel signatures in these tumors. We observed tumor heterogeneity in these tumors coming from the same metastatic tissue site across different patients while the different metastatic tumor sites coming from the same patient are more homogenous in nature.

PROVIDER: phs001658 | dbGaP |

REPOSITORIES: dbGaP

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			Action	DRS
	GapExchange_phs001658.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	Study_Report.phs001658.AdrenocorticalCarcinoma.v1.p1.MULTI.pdf	Pdf
	manifest_phs001658.AdrenocorticalCarcinoma.v1.p1.c1.GRU.pdf	Pdf
	datadict_v2.xsl	Other

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Project description:Prostate cancer is characterized by heterogeneity in the clinical course that often does not to correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer, and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets. Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors. The metastatic samples are highly heterogeneous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodeling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1). We hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer. Experiment Overall Design: Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors.

Dataset Information

Tumor Heterogeneity in Metastatic Adrenocortical Tumors

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