LINE-I element insertion at the t(11;22) translocation breakpoint of a desmoplastic small round cell tumor

Li, Jun; Nau, Marion M.; Zucman‐Rossi, Jessica; Powell, John; Allegra, Carmen J.; Wright, John J.

doi:10.1002/(sici)1098-2264(199703)18:3<232::aid-gcc10>3.0.co;2-k

Cited by 38 publications

(31 citation statements)

References 39 publications

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“…The significance of this insertion is not known, however, it may suggest a transposition during the translocation process. A similar finding was reported in desmoplastic small round cell tumor with a 480 bp heterologous DNA segment with homology to the LINE-1 DNA consensus sequence inserted at the genomic breakpoint (Liu et al, 1997).…”

Section: Discussionsupporting

confidence: 82%

Characteristic sequence motifs located at the genomic breakpoints of the translocation t(X;18) in synovial sarcomas

et al. 2003

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The SYT-SSXI and SYT-SSX2 fusion genes, derived by reciprocal translocations t(X;18), are acquired genetic events strongly associated with the tumorigenesis of synovial sarcoma. In approaching the mechanisms underlying the formation of these fusion oncogenes, we have analysed the genomic sequences surrounding the SYT-SSX breakpoints in 10 tumors, two expressing SYT-SSXI and eight expressing SYT-SSX2 fusion transcripts. The breakpoints were found to be clustered in the 5 0 end of intron 10 of SYT, and in two cluster regions within intron 4 of SSX2, whereas the two breakpoints in SSX1 intron 4 were 0.5 kb apart. SYT intron 10 is abundant in repetitive regions with the interspersed repeats occupying 66% of the whole intron. Nine of the 10 breakpoints in intron 10 of SYT and six of the eight breakpoints in intron 4 of SSX2 were at or near repetitive regions. These findings suggest that repetitive regions may contribute to the distribution of genomic breakpoints. Several of the fusion sequences exhibited characteristic signs of nonhomologous end joining, including microhomologies at the end points as well as deletions. Sequences highly homologous (83-94%) to consensus topoisomerase II cleavage sites were identified at or near the breakpoints in all 10 tumors, suggesting a role of this enzyme in creating staggered ends at the breakpoint. Furthermore, sequences highly homologous to consensus Translin binding sequences were found at the breakpoints in two cases, and an Alu-Alu fusion and an insertion of a 206-bp LINE-1 element were found at the breakpoint in one case each. The demonstration of characteristic sequences at the SYT-SSX breakpoint regions is expected to improve our understanding of the molecular genetic mechanisms behind translocations in general, and of the SYT-SSX fusions in synovial sarcoma in particular.

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Section: Discussionsupporting

confidence: 82%

Characteristic sequence motifs located at the genomic breakpoints of the translocation t(X;18) in synovial sarcomas

et al. 2003

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“…Retrotransposition of LINE-1 sequences results in a highly unstable branched DNA structure prone to undergoing recombination with accessible elements located nearby or even elsewhere in the genome (Feng et al, 1996). Chromosome deletions and translocations probably caused by retrotransposition events have indeed been observed in several human cancers (Morse et al, 1988;Nagarajan et al, 1990;Miki et al, 1992;Pomykala et al, 1994;Liu et al, 1997). The decrease in promoter methylation in urothelial tumour cells and the occurrence of full-length LINE-1 transcripts in two bladder carcinoma cell lines with hypomethylated DNA (Figure 6) raises the possibility of retrotransposition occurring in urothelial carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…Disruption of genes by insertion of LINE-1 elements has been found in human cancer and genetic disease (Morse et al, 1988;Miki et al, 1992;Dombroski et al, 1993;Holmes et al, 1994). In addition, DNA methylation and expression of LINE-1 and HERV-K provirus sequences in urothelial and renal cell carcinomas LINE-1 sequences have been identified at or near chromosomal translocation sites (Nagarajan et al, 1990;Pomykala et al, 1994;Liu et al, 1997). Presumably to prevent such accidents, most elements are highly methylated in normal adult tissues (Alves et al, 1996;Jürgens et al, 1996;Woodcock et al, 1997).…”

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confidence: 99%

DNA methylation and expression of LINE-1 and HERV-K provirus sequences in urothelial and renal cell carcinomas

et al. 1999

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Summary Since DNA methylation is considered an important mechanism for silencing of retroelements in the mammalian genome, hypomethylation in human tumours may lead to their reactivation. The methylation status of LINE-1 retroposons was determined in 73 samples of urinary bladder cancers, 34 specimens of renal cell carcinoma and in the corresponding normal tissues by Southern blot analysis. LINE-1 sequences were strongly methylated in normal tissues and were significantly hypomethylated in 69 (95%) urothelial carcinomas, but in none of the renal carcinomas. Hypomethylation in bladder cancers was independent of stage and tended to increase with grade. The methylation status of HERV-K proviral DNA in normal and transformed urothelial cells paralleled that of LINE-1 sequences (r 2 = 0.87). It was shown by ligation-mediated polymerase chain reaction that hypomethylation also extended to the LINE-1 promoter sequence located at the 5′-ends of full-length elements which is repressed by methylation in somatic tissues. Accordingly, full-length LINE-1 transcripts were detected by Northern blot analysis in two urothelial carcinoma cell lines. In contrast, transcripts from HERV-K proviruses were restricted to teratocarcinoma cell lines. Our data indicate that genome-wide DNA hypomethylation is an early change in urothelial carcinoma, but is absent from renal cell carcinoma. The coordinate changes of LINE-1 and HERV-K DNA methylation suggest that hypomethylation in urothelial cancer affects a variety of different retroelements to similar extents. We speculate that decreased methylation of LINE-1 retroelements, in particular, may contribute to genomic instability in specific human tumours such as urothelial carcinoma by rendering these normally repressed sequences competent for transcription and recombination.

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“…To exert such effect on neighboring genes, retrotransposons need not necessarily be full-length, nor retrotransposition-competent, but simply endowed with functional promoter elements [28] . Previous studies have shown that some non-full length L1 elements (even shorter than 500 bp) may yield L1 products such as L1 RNA or active RT [29][30][31] . L1 RNAs are also involved in extensive RNA splicing that can radically alter the diversity of expressed RNA forms from these elements, as well as influence their impact on gene expression upon genomic insertion [32] .…”

Section: Discussionmentioning

confidence: 99%

LINE-1 family member GCRG123 gene is up-regulated in human gastric signet-ring cell carcinoma

Wang

Wang²,

Wu³

et al. 2008

WJG

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AIM:To analyze the expression profiles of a human gastriccancer-related gene, GCRG123 , in human gastric signetring cell carcinoma tissues, and to perform bioinformatics analysis on GCRG123 . METHODS:In situ hybridization was used to explore the GCRG123 expression pattern in paraffin-embedded gastric tissues, including 15 cases of signet-ring cell carcinoma, 15 of intestinal-type adenocarcinoma, and 15 of normal gastric mucosa. Northern blotting was used to analyze the differences in GCRG123 expression between stomach signet-ring cell carcinoma and intestinal-type adenocarcinoma tissues. Online software, including BLAST, Multalin and BLAT, were applied for bioinformatics analysis. National Center for Biotechnology Information (NCBI) and the University of California Santa Cruz (UCSC) databases were used for the analyses. RESULTS:The in situ hybridization signal appeared as blue precipitates restricted to the cytoplasm. Ten out of 15 cases of gastric signet ring cell carcinoma, normal gastric mucosal epithelium and pyloric glands showed high GCRG123 expression. Low GCRG123 expression was observed in gastric intestinal-type adenocarcinoma and normal gastric glands. Northern blotting revealed that GCRG123 was up-regulated in signet-ring cell carcinoma tissue but down-regulated in intestinal-type adenocarcinoma tissue. BLAST and Multalin analyses revealed that the GCRG123 sequence had 92% similarity with the ORF2 sequence of human long interspersed nuclear element retrotransposons (LINE-1, L1).BLAT analysis indicated that GCRG123 mapped to all chromosomes. GCRG123 was found to integrate in the intron-17 and -23 of Rb, 5' flanking region of IL-2 and clotting factor Ⅸ genes. LINE-1 family member GCRG123 gene is up-regulated in human gastric signet-ring cell carcinoma. World

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LINE-I element insertion at the t(11;22) translocation breakpoint of a desmoplastic small round cell tumor

Cited by 38 publications

References 39 publications

Characteristic sequence motifs located at the genomic breakpoints of the translocation t(X;18) in synovial sarcomas

Characteristic sequence motifs located at the genomic breakpoints of the translocation t(X;18) in synovial sarcomas

DNA methylation and expression of LINE-1 and HERV-K provirus sequences in urothelial and renal cell carcinomas

LINE-1 family member GCRG123 gene is up-regulated in human gastric signet-ring cell carcinoma

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