title: Molecular cytogenetic analysis of clustered sporadic and familial renal cell carcinoma-associated 3q13 approximately q22 breakpoints.
abstract: We describe several relatives within one renal cell cancer (RCC) family sharing a constitutional t(2;3) (q35;q21). Based on molecular studies on several independent primary tumors in this family, a causative role for this translocation in tumor development was suggested. Subsequent positional cloning of the 3q21 chromosomal breakpoint revealed that this breakpoint disrupts a novel gene, DIRC2 (disrupted in renal cancer 2). This gene encodes an evolutionary conserved transmembrane protein and represents a novel member of the MFS superfamily of transporters. To evaluate whether DIRC2 is also targeted in sporadic RCC cases with cytogenetically defined 3q21 breakpoints, fluorescence in situ hybridization analysis was performed on metaphase spreads and/or interphase nuclei of 12 primary sporadic RCC using genomic clones from a 3q21 breakpoint-spanning contig as probes. Three breakpoints were mapped proximal to the familial breakpoint and nine breakpoints were mapped distal to this breakpoint. Two of the latter breakpoints were mapped in the contig within 1 Mb distance from the familial breakpoint. Because these clustered 3q21 breakpoints do not coincide with the familial 3q21 breakpoint, they most likely affect genes distinct from DIRC2.
authors.affiliation: Department of Human Genetics, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands. D.Bodmer@antrg.azn.nl
authors.forename: Daniëlle
authors.initials: D
authors.lastname: Bodmer
authors.forename: Irene
authors.initials: I
authors.lastname: Janssen
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Jonkers
authors.forename: Eva
authors.initials: E
authors.lastname: van den Berg
authors.forename: Trijnie
authors.initials: T
authors.lastname: Dijkhuizen
authors.forename: Maria
authors.initials: M
authors.lastname: Debiec-Rychter
authors.forename: Eric
authors.initials: E
authors.lastname: Schoenmakers
authors.forename: Ad Geurts
authors.initials: AG
authors.lastname: van Kessel
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000235:genetics*; D014178:Translocation, Genetic