Chromophobe renal cell carcinoma with and without sarcomatoid change: a clinicopathological, comparative genomic hybridization, and whole-exome sequencing study.

ABSTRACT: Chromophobe renal cell carcinomas (CRCC) with and without sarcomatoid change have different outcomes; however, fewstudies have compared their genetic profiles. Therefore, we identified the genomic alterationsin CRCC common type (CRCC C) (n=8) and CRCC with sarcomatoid change (CRCC S) (n=4) using comparative genomic hybridization (CGH) and whole-exome sequencing. The CGH profiles showed that the CRCC C group had more chromosomal losses (72 vs. 18) but fewer chromosomal gains (23 vs. 57) than the CRCC S group. Losses of chromosomes 1p, 8p21-23, 10p16-20, 10p12-ter, 13p20-30, and 17p13 and gains of chromosomes 1q11, 1q21-23, 1p13-15, 2p23-24, and 3p21-ter differed between the groups. Whole-exome sequencing showed that the mutational status of 270 genes differed between CRCC (n=12) and normal renal tissues (n=18). In the functional enrichment analysis, the missense-mutated genes were classified into 6 biological processes (38 functions) and 5 pathways. The biological processes included cell adhesion, cell motility, ATP metabolism, sensory perception, carbohydrate and lipid metabolism and transport. The pathways included ATP-binding cassette transporter, extracellular matrix-receptor interaction, olfactory transduction, chondroitin sulfate biosynthesis, and hypertrophic cardiomyopathy. Whole-exome sequencing analysis revealed that the missense mutation statuses of 49 genes differed between the CRCC C and CRCC S groups. Furthermore, genetic alterations in metastasis suppressor 1, serine peptidase inhibitor Kazal type 8, transient receptor potential cation channel super family M member 6, Rh family B glycoprotein, and mannose receptor C type 1 were located in different chromosomal regions. These alterations may provide clues regarding CRCC tumorigenesis and provide a basis for future targeted therapies.

SUBMITTER: Ren Y 

PROVIDER: S-EPMC4697725 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature