Translin recognition site sequences flank chromosome translocation breakpoints in alveolar rhabdomyosarcoma cell lines

Chalk, Jeremy; Barr, Frederic G.; Mitchell, Christopher

doi:10.1038/sj.onc.1201285

Cited by 32 publications

(28 citation statements)

References 13 publications

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“…In two tumors (cases 2 and 3), the breakpoint sequence showed strong homology to the consensus binding site sequence of Translin. Translin is a protein involved in recombination and translocations, as it not only binds to translocation breakpoint sequences in hematopoietic malignancies but also binds to translocation breakpoints in alveolar rhabdomyosarcomas and liposarcomas (Aoki et al, 1995;Chalk et al, 1997;Hosaka et al, 2000). The degress of homology to consensus Translin-binding sites observed in this study (71 and 75%, respectively) was in accordance to those reported previously in liposarcomas (more than 70%), but higher than those reported in alveolar rhabdomyosarcomas (62%).…”

Section: Discussionsupporting

confidence: 90%

“…Some features, including Translin recognition sites, topoisomerase II cleavage sites, Alu repeats, palindromic sequences and other characteristic motifs, have been identified near the genomic breakpoints in alveolar rhabdomyosarcoma, myxoid liposarcoma and some cases of Ewing's sarcoma (Chalk et al, 1997;Panagopoulos et al, 1997;Barr et al, 1998;Ishida et al, 1998;Kanoe et al, 1999). Although progress on the diagnostic utilities and functions of the SYT-SSX fusion gene in synovial sarcomas has been made in recent years, studies concerning the mechanisms underlying the t(X;18) chromosomal translocation have not, to our knowledge, been reported.…”

Section: Discussionmentioning

confidence: 99%

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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: 90%

Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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“…We showed that liposarcoma is the second solid tumor next to rhabdomyosarcoma (Chalk et al, 1997), of which the breakpoint sequences are shown to bind Translin by mobility-shift assay. In the case of Ewing's sarcoma, two recent studies denied the presence of Translin binding motifs at the breakpoints (ZucmanRossi et al, 1998;Obata et al, 1999).…”

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confidence: 97%

“…Among them was Translin, which was originally isolated as a protein binding to a common sequence motif at the 5'¯anking region of breakpoints in 91 lymphoid malignancies consisted of 16 di erent types (Aoki et al, 1995). Following studies have revealed that similar motif also existed at the breakpoints in several other neoplasms with reciprocal translocations speci®c for each type of tumor, such as chronic myeloid leukemia, acute myeloid leukemia, and alveolar rhabdomyosarcoma (Atlas et al, 1998;Je s et al, 1998;Chalk et al, 1997). However, the location relative to the breakpoints and the degree of homology with consensus sequences varied considerably among each`putative Translin binding sequence', making it di cult to compare the results of di erent studies.…”

mentioning

confidence: 99%

“…In addition, regions to be searched for Translin binding motif are also to be de®ned. As in the original study in lymphoid malignancies, following studies concentrated on the analysis of the sense strand sequences around the breakpoints to ®nd Translin binding motifs (Atlas et al, 1998;Je s et al, 1998;Chalk et al, 1997). However, Translin was shown to bind single strand DNA (Kasai et al, 1997), which will be created as a staggered end after chromosomal breakage.…”

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Translin binds to the sequences adjacent to the breakpoints of the TLS and CHOP genes in liposarcomas with translocation t(12;16)

et al. 2000

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Myxoid and round-cell liposarcomas share the translocation t(12;16)(q13;p11) creating the TLS-CHOP fusion gene as a common genetic alteration. We previously reported several unique characteristics of genomic sequences around the breakpoints in the TLS and CHOP loci, and among them was the presence of consensus recognition motifs of Translin, a protein that associates with chromosomal translocations of lymphoid neoplasms. We further extended our search for Translin binding motifs in sequences adjacent to breakpoints and investigated whether Translin binds to these sequences in vitro by mobility-shift assay. Computer-assisted search found sequences highly homologous (470%) with Translin binding motifs adjacent to the breakpoints in 10 out of 11 liposarcomas with the TLS-CHOP fusion genes. All of 13 oligonucleotides corresponding to the putative binding sequences in these cases bind to Hela cell extract and also recombinant Translin protein, although the binding a nity of each motif showed considerable di erences. The DNA-protein complex formation was inhibited by non-labeled competitor or anti-Translin antibody, suggesting the speci®city of the complex formation. Considering the high incidence and speci®c binding property, the presence of Translin binding motif may be one of the important determinants for the location of breakpoints in the TLS and CHOP genes in liposarcomas. Oncogene (2000) 19, 5821 ± 5825.

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3?BCR recombines withIGL locus inBCR-ABL-positive Philadelphia-negative chronic myeloid leukemia

Benjes

Millow

Jeffs

et al. 1999

Genes Chromosom. Cancer

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We have isolated the 3′ BCR breakpoint junction of a complex BCR‐ABL1 rearrangement found in leukemic cells with a cytogenetically normal karyotype, and the corresponding germline fragment that spanned the 3′ BCR recombination site. Fluorescence in situ hybridization localized the 3′ BCR recombination site to 22q11, about 350–600 kb proximal to BCR. Restriction map and DNA sequence comparisons indicated that 3′ M‐Bcr had recombined at a site within the variable region (Itv Region IV) of the immunoglobulin lambda (IGL) locus. Somatic rearrangement of DNA sequences (variable, joining, and constant regions) within the IGL locus, as in other Ig and TCR loci, represents the basis for human antibody diversity. Misrecombination of these somatically rearranging sites has been associated with chromosomal rearrangements in lymphoid leukemia and lymphoma, but there are no previous descriptions of IGL involvement in genomic aberrations associated with myeloid leukemia. Genes Chromosomes Cancer 26:366–371, 1999. © 1999 Wiley‐Liss, Inc.

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Translin recognition site sequences flank chromosome translocation breakpoints in alveolar rhabdomyosarcoma cell lines

Cited by 32 publications

References 13 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

Translin binds to the sequences adjacent to the breakpoints of the TLS and CHOP genes in liposarcomas with translocation t(12;16)

3?BCR recombines withIGL locus inBCR-ABL-positive Philadelphia-negative chronic myeloid leukemia

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