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

Krill-Burger JM, Lyons MA, Kelly LA, Sciulli CM, Petrosko P, Chandran UR, Kubal MD, Bastacky SI, Parwani AV, Dhir R, LaFramboise WA. Renal cell neoplasms contain shared tumor type-specific copy number variations. Am J Pathol. 2012 Jun; 180(6):2427-39. doi: 10.1016/j.ajpath.2012.01.044. Epub 2012 Apr 3. PMID: 22483639. PMCID: PMC3378847.

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.

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2012
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Krill-Burger JM, Lyons MA, Kelly LA, Sciulli CM, Petrosko P, Chandran UR, Kubal MD, Bastacky SI, Parwani AV, Dhir R, LaFramboise WA
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