title: Unclassified renal cell carcinoma: a clinicopathological, comparative genomic hybridization, and whole-genome exon sequencing study.
abstract: Unclassified renal cell carcinoma (URCC) is a rare variant of RCC, accounting for only 3-5% of all cases. Studies on the molecular genetics of URCC are limited, and hence, we report on 2 cases of URCC analyzed using comparative genome hybridization (CGH) and the genome-wide human exon GeneChip technique to identify the genomic alterations of URCC. Both URCC patients (mean age, 72 years) presented at an advanced stage and died within 30 months post-surgery. Histologically, the URCCs were composed of undifferentiated, multinucleated, giant cells with eosinophilic cytoplasm. Immunostaining revealed that both URCC cases had strong p53 protein expression and partial expression of cluster of differentiation-10 and cytokeratin. The CGH profiles showed chromosomal imbalances in both URCC cases: gains were observed in chromosomes 1p11-12, 1q12-13, 2q20-23, 3q22-23, 8p12, and 16q11-15, whereas losses were detected on chromosomes 1q22-23, 3p12-22, 5p30-ter, 6p, 11q, 16q18-22, 17p12-14, and 20p. Compared with 18 normal renal tissues, 40 mutated genes were detected in the URCC tissues, including 32 missense and 8 silent mutations. Functional enrichment analysis revealed that the missense mutation genes were involved in 11 different biological processes and pathways, including cell cycle regulation, lipid localization and transport, neuropeptide signaling, organic ether metabolism, and ATP-binding cassette transporter signaling. Our findings indicate that URCC may be a highly aggressive cancer, and the genetic alterations identified herein may provide clues regarding the tumorigenesis of URCC and serve as a basis for the development of targeted therapies against URCC in the future.
authors.affiliation: Department of Pathology, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China Xinjiang 832002, China.
authors.forename: Zhen-Yan
authors.initials: ZY
authors.lastname: Hu
authors.affiliation: Department of Pathology, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China Xinjiang 832002, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Pang
authors.affiliation: Department of Pathology, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China Xinjiang 832002, China ; Tongji Hospital Cancer Center, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Pathology, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China Xinjiang 832002, China.
authors.forename: Xue-Ling
authors.initials: XL
authors.lastname: Kang
authors.affiliation: Department of Pathology, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China Xinjiang 832002, China ; Tongji Hospital Cancer Center, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Hu
authors.affiliation: Department of Pathology, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China Xinjiang 832002, China.
authors.forename: Lianghai
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China Xinjiang 832002, China.
authors.forename: Kun-Peng
authors.initials: KP
authors.lastname: Liu
authors.affiliation: Department of Pathology, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China Xinjiang 832002, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Pathology, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China Xinjiang 832002, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Pathology, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China Xinjiang 832002, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Song
authors.affiliation: Department of Pathology, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China Xinjiang 832002, China.
authors.forename: Hong-An
authors.initials: HA
authors.lastname: Li
authors.affiliation: Department of Pathology, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China Xinjiang 832002, China ; Tongji Hospital Cancer Center, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Pathology, School of Medicine, Shihezi University, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education of China Xinjiang 832002, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D015894:Genome, Human; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis
keywords: Unclassified renal cell carcinoma; chromosome imbalance; comparative genomic hybridization; exon GeneChip; gene mutation