The human minisatellite consensus at breakpoints of oncogene translocations

Krowczynska, Anna; Rudders, Richard A.; Krontiris, Theodore G.

doi:10.1093/nar/18.5.1121

Cited by 110 publications

(63 citation statements)

References 35 publications

(20 reference statements)

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“…Alu interspersed sequence elements have been found close to or at the breakpoints in Philadelphia (Ph) chromosome positive chronic myeloid leukemia and acute lymphoblastic leukemia and may be involved in homologous or non-homologous recombinations leading to the formation of the Ph chromosome (de Klein et al, 1986;Papadopoulos et al, 1990) (Krowczynska et al, 1990). Finally, topoisomerase II may be involved.…”

Section: Resultsmentioning

confidence: 99%

Characteristic sequence motifs at the breakpoints of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in myxoid liposarcoma and acute myeloid leukemia

et al. 1997

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We have sequenced the breakpoint regions in one acute myeloid leukemia (AML) with t(16;21)(p11;q22) resulting in the formation of a FUS/ERG hybrid gene and in four myxoid liposarcomas (MLS), three of which had the translocation t(12;16) (q13;p11) and a FUS/CHOP fusion gene and one with t(12;22;20)(q13;q12;q11) and an EWS/CHOP hybrid gene. The breakpoints were localized to intron 7 of FUS, intron 1 of CHOP, an intronic sequence of ERG and intron 7 of EWS. In two MLS cases with t(12;16) and in the AML, the breaks in intron 7 of FUS had occurred close to each other, a few nucleotides downstream from a TG dinucleotide repeat region. The break in the two MLS had occurred in the same ATGGTG hexamer and in the AML 40 nucleotides upstream from the hexamer. The third case of t(12;16) MLS had a break upstream and near a TCdinucleotide repeat region and a sequence similar to the chi bacterial recombination element was found tō ank the breakpoint. In the MLS with the EWS/ CHOP hybrid gene, the break in intron 7 of EWS had occurred close to an Alu sequence. Similarly, in all 4 MLS, the breaks in intron 1 of CHOP were near an Alu sequence. No Alu or other repetitive sequences were found 250 bp upstream or downstream from the break in the ERG intron involved in the AML case. In the AML, the MLS with ESW/CHOP and in one MLS with FUS/CHOP there were one, two and six, respectively, nucleotide identity between the contributing germline sequences in the breakpoint. In the other two MLS cases, two and three extra nucleotides of unknown origin were inserted between the FUS and CHOP sequences. At the junction and/or in its close vicinity, identical oligomers, frequently containing a trinucleotide TGG, were found in both partner genes. Our data thus show that all four genes-FUS, EWS, CHOP and ERG-contain characteristic motifs in the breakpoint regions which may serve as speci®c recognition sites for DNA-binding proteins and have functional importance in the recombination events taking place between the chromosomes. Di erent sequence motifs may, however, play a role in each individual case.

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Section: Resultsmentioning

confidence: 99%

Characteristic sequence motifs at the breakpoints of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in myxoid liposarcoma and acute myeloid leukemia

et al. 1997

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“…Such an element could be a Chi element, a short sequence that is often located in the vicinity of breakpoints. Chi or Chi-like elements are thought to play a major part in recombination processes (43) and may also be involved in replication slippage (44). At position 2626, immediately 5' of the breakpoint of patient 2, a Chi-like sequence is present (GGTGGAGG; Table 1) and could cause a DNA break.…”

Section: Discussionmentioning

confidence: 99%

Hotspot for deletions in the CGG repeat region of FMR1 in fragile X patients

Graaff¹,

Rouillard

Willems

et al. 1995

Human Molecular Genetics

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The fragile X syndrome is the most frequent cause of inherited mental retardation. The molecular mechanism of the disorder is based on the expansion of a CGG repeat in the 5' UTR of the FMR1 gene in the majority of fragile X patients. The instability of this CGG repeat containing region is not restricted to the CGG repeat itself but expands to the flanking region as well. We describe four unrelated fragile X patients that are mosaic for both a full mutation and a small deletion in the CGG repeat containing region. Sequence analysis of the regions surrounding the deletions showed that both the (CGG)n repeat and some flanking sequences were missing in all four patients. The 5' breakpoints of the deletions were found to be located between 75-53 bp proximal to the CGG repeat. This suggests the presence of a hot spot region for deletions in the CGG repeat region of the FMR1 gene and emphasizes the instability of this region in the presence of an expanded CGG repeat.

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“…The sequences around the breakpoint in each case were compared with following sequences which have been considered to be involved in the process of chromosomal rearrangements; Chi-like octamers (GC[A/T]GG[A/T]GG) (Krowczynska et al, 1990;Sowerby et al, 1993), immunoglobulin heptamers (GATAGTG) (Cheng et al, 1989), a-protein recognition sites (AAATATC and TTAATTC), topoisomerase II recognition sites (topoIIv, (Aoki et al, 1995).…”

Section: Sequence Analyses With Data Basementioning

confidence: 99%

Characteristics of genomic breakpoints in TLS-CHOP translocations in liposarcomas suggest the involvement of Translin and topoisomerase II in the process of translocation

et al. 1999

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Fusion of TLS/FUS and CHOP gene by reciprocal translocation t(12;16)(q32;q16) is a common genetic event found in myxoid and round-cell liposarcomas. Characterization of this genetic event was performed by three methods, Southern blot, RT ± PCR, and genomic long-distance PCR in nine myxoid and three round-cell liposarcomas. All but one tumors showed genetic alternations indicating the fusion of TLS/FUS and CHOP gene. Two novel types of fusion transcripts were found, of which one lacked exon 2 sequence of CHOP gene, and the other lacked 3' half of exon 5 of TLS gene. The latter case was caused by a cryptic splicing site which was created by the genomic fusion. Detailed analyses genomic fusion points revealed several sequence characteristics surrounding the fusion points. Homology analyses of breakpoint sequences with known sequence motifs possibly involve in the process of translocation uncovered Translin binding sequences at both of TLS/ FUS and CHOP breakpoints in two cases. Translocations were always associated with other genetic alterations, such as deletions, duplications, or insertions. Short direct repeats were almost always found at both ends of deleted or duplicated fragments some of which had apparently been created by joining of sequences that ank the rearrangement. Finally, consensus topoisomerase II cleavage sites were found at breakpoints in all cases analysed, suggesting a role of this enzyme in creating staggered ends at the breakpoint. These data suggested that sequence characteristics may play an important role to recruit several factors such as Translin and topoisomerase II in the process of chromosomal translation in liposarcomas.

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The human minisatellite consensus at breakpoints of oncogene translocations

Cited by 110 publications

References 35 publications

Characteristic sequence motifs at the breakpoints of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in myxoid liposarcoma and acute myeloid leukemia

Characteristic sequence motifs at the breakpoints of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in myxoid liposarcoma and acute myeloid leukemia

Hotspot for deletions in the CGG repeat region of FMR1 in fragile X patients

Characteristics of genomic breakpoints in TLS-CHOP translocations in liposarcomas suggest the involvement of Translin and topoisomerase II in the process of translocation

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