Renal cell neoplasms contain shared tumor type-specific copy number variations.

Abstract

Copy number variant (CNV) analysis was performed on renal cell carcinoma (RCC) specimens (chromophobe, clear cell, oncocytoma, papillary type 1, and papillary type 2) using high-resolution arrays (1.85 million probes). The RCC samples exhibited diverse genomic changes within and across tumor types, ranging from 106 to 2238 CNV segments in a clear-cell specimen and in a papillary type 2 specimen, respectively. Despite this heterogeneity, distinct CNV segments were common within each tumor classification: chromophobe (seven segments), clear cell (three segments), oncocytoma (nine segments), and papillary type 2 (two segments). Shared segments ranged from a 6.1-kb deletion (oncocytomas) to a 208.3-kb deletion (chromophobes). Among common tumor type-specific variations, chromophobes, clear-cell tumors, and oncocytomas were composed exclusively of noncoding DNA. No CNV regions were common to papillary type 1 specimens, although there were 12 amplifications and 12 deletions in five of six samples. Three microRNAs and 12 mRNA genes had a ≥98% coding region contained within CNV regions, including multiple gene families (chromophobe: amylases 1A, 1B, and 1C; oncocytoma: general transcription factors 2H2, 2B, 2C, and 2D). Gene deletions involved in histone modification and chromatin remodeling affected individual subtypes (clear cell: SFMBT and SETD2; papillary type 2: BAZ1A) and the collective RCC group (KDM4C). The genomic amplifications/deletions identified herein represent potential diagnostic and/or prognostic biomarkers.

• Authors: John M Krill-Burger, Maureen A Lyons, Lori A Kelly, Christin M Sciulli, Patricia Petrosko, Uma R Chandran, Michael D Kubal, Sheldon I Bastacky, Anil V Parwani, Rajiv Dhir, William A LaFramboise
• Journal: The American journal of pathology (Am J Pathol) Vol. 180 Issue 6 Pg. 2427-39 (Jun 2012) ISSN: 1525-2191 [Electronic] United States
• PMID: 22483639 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• DNA, Neoplasm
• MicroRNAs
• RNA, Messenger
• RNA, Neoplasm

Topics

• Carcinoma, Papillary (genetics, pathology)
• Carcinoma, Renal Cell (genetics, pathology)
• DNA Copy Number Variations
• DNA, Neoplasm (genetics)
• Gene Amplification
• Gene Deletion
• Genes, Neoplasm
• Humans
• Kidney Neoplasms (genetics, pathology)
• MicroRNAs (genetics)
• Polymorphism, Single Nucleotide
• RNA, Messenger (genetics)
• RNA, Neoplasm (genetics)