title: Characterization of t(6;11)(p21;q12) in a renal-cell carcinoma of an adult patient.
abstract: Renal-cell carcinoma (RCC) constitutes a heterogeneous group of tumors with specific chromosome aberrations. Recently, a new small group of RCC, occurring in children and young adults, has been described as characterized by t(6;11)(p21;q12). It has been shown that this translocation results in the fusion of the 5' portion of the ALPHA gene (11q12) with the transcription factor gene TFEB (6p21). Herewith, we report the first complete cytogenetic and molecular characterization of a t(6;11)-positive RCC of an adult patient, a 54-year-old woman. The tumor was histologically defined as RCC with peculiar features and it was negative for epithelial markers and positive for melanocytic markers. Chromosome QFQ banding analysis of short-term cultured cells from the RCC showed t(6;11)(p21;q12) as the sole cytogenetic abnormality. The translocation was confirmed by FISH analysis. RT-PCR analysis, performed on total RNA isolated from both neoplastic and normal tissue samples, revealed an ALPHA-TFEB chimeric transcript in the tumor sample; sequencing of the RT-PCR product defined a novel TFEB gene breakpoint cluster region, broader than the one reported thus far. Western blot analysis showed a band at the expected size of wild-type TFEB in the neoplastic tissue compared to the normal sample, supporting that the fusion gene does not encode for a chimeric protein but it causes an upregulation of the wild-type TFEB. Our data contribute to define better this rare RCC type, which is typical not only of childhood but can also be found in adulthood.
authors.affiliation: Department of Pathology, Scientific Institute San Raffaele Hospital, Milano, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pecciarini
authors.forename: M Giulia
authors.initials: MG
authors.lastname: Cangi
authors.forename: Crocifissa
authors.initials: C
authors.lastname: Lo Cunsolo
authors.forename: Ettore
authors.initials: E
authors.lastname: Macri'
authors.forename: Elena
authors.initials: E
authors.lastname: Dal Cin
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000737:chemistry / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002896:Chromosomes, Human, Pair 6; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D017931:DNA Primers; D009363:Neoplasm Proteins; C064972:TFEB protein, human