title: Genetic alterations in renal cell carcinoma with rhabdoid differentiation.
abstract: Renal cell carcinoma with rhabdoid differentiation (RCC-R) in adult patients is an aggressive variant of renal cancer with no known specific genetic alterations. The aim of this study was to characterize genome-wide genetic aberrations in RCC-R via utilization of high-density single-nucleotide polymorphism (SNP) arrays. We identified 20 cases of RCC-R, which displayed both clear cell renal cell carcinoma and rhabdoid histomorphologic components. DNA was extracted from formalin-fixed, paraffin-embedded tissue (from clear cell renal cell carcinoma and RCC-R areas from each case) and subjected to high-density SNP array assay. Genetic aberrations present in 10% of cases were considered significant. In areas with clear cell histomorphology, gains were most commonly observed in chromosomes 5q (66.7%, 10/15), 7 (46.7%, 7/15), and 8q (46.7%, 7/15); and losses were most commonly identified in chromosomes 14 (60%, 9/15), 8p (46.7%, 7/15), and 22 (46.7%, 7/15). In areas with rhabdoid differentiation, gains were most commonly observed in chromosome 7 (58.8%, 10/17); and losses were most commonly identified in chromosomes 9 (70.6%, 12/17), 14 (58.8%, 10/17), 4 (52.9%, 9/17), and 17p (52.9%, 9/17). Rhabdoid cells shared many chromosomal abnormalities and exhibited a greater number of copy number variations in comparison with coexisting clear cells. Loss of 11p was specific for rhabdoid differentiation, with loss found in 29.4% of rhabdoid components compared with 0% of clear cell areas. The greater number of overall genetic alterations in the rhabdoid cells and the shared genetic background between rhabdoid and clear cell areas suggest genetic evolution of the rhabdoid cells that correlates with histomorphologic progression.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Perrino
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
authors.forename: Vishwanathan
authors.initials: V
authors.lastname: Hucthagowder
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Evenson
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
authors.forename: Shashikant
authors.initials: S
authors.lastname: Kulkarni
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT, 06520-8023, USA. Electronic address: peter.humphrey@yale.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Humphrey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics*; D002869:Chromosome Aberrations; D002877:Chromosomes, Human; D056915:DNA Copy Number Variations; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018335:Rhabdoid Tumor / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor
keywords: Genetics; Kidney; Renal cell carcinoma; Rhabdoid; SNP array