Histopathologic subtype-specific genomic profiles of renal cell carcinomas identified by high-resolution whole-genome single nucleotide polymorphism array analysis

Abstract

Abstract.To elucidate the novel and common genetic changes in histopathologic subtype-specific profiles of renal cell carcinomas (RCCs), a newly developed high-resolution wholegenome array analysis was applied. Human CNV370-Duo DNA Analysis BeadChip (genotype 370K) was used in a panel of 22 primary clear cell RCCs (ccRCCs), seven papillary RCCs (PRCCs) (six type II and one type I) and eight chromophobe RCCs (ChRCCs). In ccRCC, a chromosome 3p loss was identified in 95% of the carcinomas, suggesting that 3p loss is the first stage in ccRCC carcinogenesis. Other frequent changes included losses of 1p (23%), 3q (46%) and 8p (32%), and gains of 5q (32%), 7p (27%), 7q (27%) and 1q (23%). The most frequent chromosomal losses in PRCC (43%) were noted in 3p and 3q, followed by 29% of losses of 1p, 1q, 11q, 18q, 22p and 22q, and gains of 20q (57%), 20p (43%), 8q (43%) and 12q (43%). Loss of the entire chromosomes 1, 2, 6, 8, 10, 13 or 17 was noted in patients with ChRCC. A high-density single nucleotide polymorphism array analysis confirmed that partial chromosomal changes rarely occur in ChRCC. Additionally, 32 microdeletions and 10 microamplifications of less than 1 Mb were detected, which may represent potential candidate tumor suppressor genes and oncogenes, respectively.

Use of quantitative shotgun proteomics to identify fibronectin 1 as a potential plasma biomarker for clear cell carcinoma of the kidney

“…We have previously reported that each RCC subtype has a totally different genetic profile by whole genome SNP array [10]. Therefore, each subtype should have a specific biomarker.…”

“…RCC consists of clear cell (75%), papillary (10%), chromophobe (5%) and other subtypes [10], and we first focused on clear cell carcinoma, the most common subtype of RCC. We discovered a significant increase of circulating plasma FN1 in patients with RCC and confirmed its significance in a larger patient cohort using a newly established measurement system.…”