title: 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.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15232, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Krill-Burger
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Lyons
authors.forename: Lori A
authors.initials: LA
authors.lastname: Kelly
authors.forename: Christin M
authors.initials: CM
authors.lastname: Sciulli
authors.forename: Patricia
authors.initials: P
authors.lastname: Petrosko
authors.forename: Uma R
authors.initials: UR
authors.lastname: Chandran
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kubal
authors.forename: Sheldon I
authors.initials: SI
authors.lastname: Bastacky
authors.forename: Anil V
authors.initials: AV
authors.lastname: Parwani
authors.forename: Rajiv
authors.initials: R
authors.lastname: Dhir
authors.forename: William A
authors.initials: WA
authors.lastname: LaFramboise
mesh_terms: D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D004273:DNA, Neoplasm / Q000235:genetics; D005784:Gene Amplification; D017353:Gene Deletion; D052138:Genes, Neoplasm; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D035683:MicroRNAs; D012333:RNA, Messenger; D012334:RNA, Neoplasm