Fine Mapping of the Human Renal Oncocytoma-Associated Translocation (5;11)(q35;q13) Breakpoint

Abstract

Recent cytogenetic analysis of a series of human renal oncocytomas revealed the presence of a recurring chromosomal translocation (5;ll)(q35;ql3) as sole anomaly in a subset of the tumors. The molecular characterization of this translocation was initiated using two primary t(5;ll)-positive renal oncocytomas and a panel of soma tic cell hybrids derived from one of these tumors, in conjunction with fluorescence in situ hybridization (FISH) and Southern blot analysis. The breakpoint in chromosome band llql3 could be located within a genomic interval of at maximum 400 Kb immediately centromeric to the BCLl locus.

Familial and Sporadic Renal Oncocytomas – A Comparative Molecular–Genetic Analysis

“…A limited number of sporadic RO were analyzed by cytogenetic and molecular techniques. These data indicate three tumor subtypes: tumors with loss of chromosomes 1/1p and in some cases combined with losses of chromosomes 14 and Y; RO with translocations involving chromosome 11, and RO with random chromosome alterations or without changes [13, 14, 15, 16, 17]. …”

“…This may point to minute chromosome alterations smaller than some megabases in size and/ or translocations both not detectable by CGH. Previous cytogenetic and molecular genetic analyses of individual RO, for example, revealed translocations involving chromosome 11 [15, 16, 17, 24]. Obviously, cases with these translocations represent a second subgroup of sporadic RO in addition to the group with losses of chromosomes 1, 14 and sex chromosomes [2, 15].…”

Renal oncocytoma with t(5;12;11), der(1)t(1;8) and add(19): “true” oncocytoma or chromophobe adenoma?

“…In these tumors, chromosome 11 is specifically translocated to either chromosome 5 or 9. The genes involved in the oncocytoma-specific 11q13 translocations are not known, but the 11q13 breakpoint has been mapped between D11S443/D11S146 and the BCL1 locus (Sinke et al, 1997).…”

“…Cosmids CcI11-44 (D11S443), BCl1-c19 and Ccl11-59 (D11S146) were used to further define the breakpoint at 11q13. These experiments were performed as described previously (Sinke et al, 1997). Cosmid cCLGW454 (D11S688) located at 11q15 served to identify chromosome 11.…”

“…At least 2 genetically defined subsets appear to emerge, characterized by (1) the combined loss of chromosomes 1 and X/Y and (2) translocations involving chromosome 11 with breakpoint 11q13. Sinke et al (1997) mapped this oncocytoma-specific 11q13 breakpoint in 2 t(5;11)-positive renal oncocytomas between D11S443/D11S146 and the BCL1 locus. The 11q13 breakpoint of a third case revealing a t(9;11)(p23;q13) has been found to be located within the same region (data not shown), suggesting that in the t(5;11)-and the t(9;11)-positive renal oncocytomas, the same gene at chromosome 11 may be involved in the development of these neoplasms.…”