Search

Renal oncocytomas reveal a considerable (cyto)genetic heterogeneity. At least 2 genetic subsets are currently recognized, characterized by (1) translocations involving breakpoint 11q13 and (2) the combined loss of chromosomes 1 and X/Y. We present a case of oncocytoma revealing a 3-way translocation involving breakpoint 11q13, a der (1)t(1;8) and an add(19). The der(1) resulted in loss of chromosome 1 sequences. Using fluorescence in situ hybridization, the 11q13 breakpoint of the present case proved to be slightly different from the one observed previously in 3 cases of renal oncocytoma. Whether the 11q13 breakpoint observed in our case resides in or near another gene remains to be elucidated. Int. J. Cancer 73:521–524, 1997. © 1997 Wiley-Liss, Inc.

A combination of Southern blot analysis on a panel of tumor-derived somatic cell hybrids and fluorescence in situ hybridization techniques was used to map YACs, cosmids and DNA markers from the Xp11.2 region relative to the X chromosome breakpoint of the renal cell carcinoma-associated t(X; 1 )(p 11 ;q21). The position of the breakpoint could be determined as follows: Xcen-OATL2-DXS146-DXS255-SYP-t(X;1)-TFE3-OATL1-Xpter. Fluorescence in situ hybridization experiments using TFE3-containing YACs and cosmids revealed split signals indicating that the corresponding DNA inserts span the breakpoint region. Subsequent Southern blot analysis showed that a 2.3-kb EcoRl fragment which is present in all TFE3 cosmids identified, hybridizes to aberrant restriction fragments in three independent t(X;1)-positive renal cell carcinoma DNAs. The breakpoints in these tumors are not the same, but map within a region of approximately 6.5 kb. Through preparative gel electrophoresis an (X;1) chimaeric 4.4-kb EcoRl fragment could be isolated which encompasses the breakpoint region present on der(X). Preliminary characterization of this fragment revealed the presence of a 150-bp region with a strong homology to the 5’ end of the mouse TFE3 cDNA in the X-chromosome part, and a 48-bp segment in the chromosome 1-derived part identical to the 5’ end of a known EST (accession number R93849). These observations suggest that a fusion gene is formed between the two corresponding genes in t(X;1)(p11;q21)-positive papillary renal cell carcinomas.

Pond snails (Lymnaea stagnalis (L.)) were treated with 2,2'-dichlorobiphenyl (DCB) or 4,4'-DCB, to examine the toxicokinetic profile of these compounds. Snails were treated orally with 210 µg 4,4'-DCB (impregnated on food) for 14 hr, or snails were injected with 50 µg of 2,2'-DCB or 4,4'-DCB in the foot. At different times after starting feeding or injection, tissues (albumen gland, digestive gland and digestive tube, central nervous system, remainder parts), hemolymph and faeces were analyzed for unchanged 2,2'- or 4,4'-DCB. The results showed that in case of oral administration of 4,4'-DCB after 144 hr, 97.5% of the dose was excreted unchanged in the faeces. During the first 48 hr 4,4'-DCB was found in all tissues. Thereafter, an exponential elimination was found (the rate constant of elimination (kel) varied from 0.010–0.021 per hr, t1/2 from 33–60 hr and the apparent clearance from 0.02–0.3 g/hr for the different tissues). After injection, the compounds were found in all the above mentioned tissues, especially in the digestive gland. There was a clear difference between snails injected with 2,2'- and 4,4'-DCB. Firstly, kel for 2,2'-DCB was higher (0.028 per hr vs 4,4'-DCB: 0.001 per hr). Secondly, 2,2'-DCB was lethal; 63% of the animals died after 72 hr.