Mapping the X chromosome breakpoint in two papillary renal cell carcinoma cell lines with a t(X;1)(p11.2;q21.2)and the first report of a female case

Abstract

A t(X;1)(p11.2;q21.2) has been reported in cases of papillary renal cell tumors arising in males. In this study two cell lines derived from this tumor type have been used to indicate the breakpoint region on the X chromosome. Both cell lines have the translocation in addition to other rearrangements and one is derived from the first female case to be reported with the t(X;1)(p11.2;q21.2). Fluorescence in situ hybridization (FISH) has been used to position YACs belonging to contigs in the Xp11.2 region relative to the breakpoint. When considered together with detailed mapping information from the Xp11.2 region the position of the breakpoint in both cell lines was suggested as follows: Xpter→Xp11.23 – OATL1 – GATA1 – WAS – TFE3 – SYP – t(X;1) – DXS255 – CLCN5 – DXS146 – OATL2 – Xp11.22→Xcen. The breakpoint was determined to lie in an uncloned region between SYP and a YAC called FTDM/1 which extends 1 Mb distal to DXS255. These results are contrary to the conclusion from previous FISH studies that the breakpoint was near the OATL2 locus, but are consistent with, and considerably refine, the position that had been established by molecular analysis.

Fusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3 gene in papillary renal cell carcinoma

“…Chromosome 1 and X paints and a probe for the pericentric region of chromosome 1 were used singly or in combination with di erentially labeled YAC probes as previously described in order to con®rm the origin of the derivative 1 and X chromosomes (Shipley et al, 1993(Shipley et al, , 1995. YAC clones for GATA and pTAK8 (Shipley et al, 1995) lie telomeric and centromeric to TFE3 at Xp11 and were labeled with green and red¯uorochromes, respectively. These YACs were cohybridised to chromosome preparations of the two cell lines and analysed as detailed previously (Shipley et al, 1993(Shipley et al, , 1995.…”

“…YAC clones for GATA and pTAK8 (Shipley et al, 1995) lie telomeric and centromeric to TFE3 at Xp11 and were labeled with green and red¯uorochromes, respectively. These YACs were cohybridised to chromosome preparations of the two cell lines and analysed as detailed previously (Shipley et al, 1993(Shipley et al, , 1995.…”

“…A high frequency of loss of chromosome Y and trisomy of chromosome 7 has, however, been reported in papillary RCC (Kovacs et al, 1987(Kovacs et al, , 1991Kovacs, 1993;van den Berg et al, 1993;Elfving et al, 1995) and a speci®c translocation between chromosomes X and 1, t(X;1)(p11.2;q21.2), has been identi®ed in cytogenetic studies (de Jong et al, 1986;Meloni et al, 1993;Mitelman, 1994;Shipley et al, 1995;Tonk et al, 1995). It has recently been shown (Sidhar et al, 1996;Weterman et al, 1996a, b) that this translocation results in the fusion of a novel chromosome 1 gene, called PRCC, to the chromosome X gene TFE3, which encodes a member of the basic-helix ± loop ± helix family of transcription factors originally identi®ed by its ability to bind to mE3 elements in the immunoglobin heavy chain intronic enhancer (Beckmann et al, 1990).…”

Cytogenetic classification of renal cell cancer

“…1 about papillary RCC showing rearrangement of the critical 3p segment, at least at a molecular level [33,34], Several hum an renal cell carcinomas with X;autosome translocations have been reported in recent years (see for review [35]], The t(X;l)(pll.2;q21) appears to be a specific primary anomaly, suggesting that tumors with this translo cation form a distinct subgroup of chromophilic RCC, showing clear cell features. These tumors preferentially occur in male patients [36][37][38][39], although one female case has recently been described [40].…”

Molecular cytogenetic analysis for TFE3 rearrangement in Xp11.2 renal cell carcinoma and alveolar soft part sarcoma: validation and clinical experience with 75 cases

“…5,16 The TFE3/ASPSCR1 involves fusion of either exon 3 or 4 of TFE3 to ASPSCR1, which replaces the N-terminus of TFE3 but retains the DNA-binding region, activation domain, and nuclear localization signal. 17 Other known partners of TFE3 include PRCC, [18][19][20] PSF, 21 NONO, 21 or CLTC 22 resulting from t(X;1)(p11.2;q21), t(X;1)(p11.2;p34), inv(X) (p11.2q12), or t(X;17)(p11.2;q23), respectively. Each of these rearrangements provides a more robust promoter for TFE3 causing overexpression of the chimeric fusion product and a subset are known to have a stronger capacity for transactivation of other genes.…”