Characterization of the rearranged tpr-met oncogene breakpoint.

Dean, Michael; Park, M; Woude, George F. Vande

doi:10.1128/mcb.7.2.921

Cited by 45 publications

(38 citation statements)

References 22 publications

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“…The breakpoints could not be precisely determined in three cases (the AML, and MLS cases L1686 and 1955 ± 91) as a result of 1, 2 and 6, respectively, nucleotide matches between the contributing germline sequences. Similar ®ndings were previously reported from the breakpoints of the human hybrid genes TPR/ MET, RET/PTC, PML/RARA and ESW/FLI1 (Bhagirath et al, 1995;Dean et al, 1987;Smanik et al, 1995;Yoshida et al, 1995). Whether or not this feature is signi®cant for somatic recombinations is unknown.…”

Section: An Octamer (Gc[a/t]gg[a/t]gg) Similar To the Chi (Gctggtggsupporting

confidence: 75%

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: An Octamer (Gc[a/t]gg[a/t]gg) Similar To the Chi (Gctggtggsupporting

confidence: 75%

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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“…Further, missense mutations that deregulate the enzymatic activity of Met have been found to be associated with human papillary renal carcinomas . Consistent with these ®ndings, Met was originally identi®ed as an oncogene, Tpr/Met (Dean et al, 1987;Gonzatti-Haces et al, 1988), which is expressed in various human tumor cell lines (Soman et al, 1990). The chimeric Tpr/Met gene, which is formed following fusion of the sequences encoding the amino-terminus of the Tpr gene and the cytoplasmic domain of the Met receptor tyrosine kinase (Dean et al, 1987), codes for a constitutively activated Met kinase possessing transforming activity (Rodrigues and Park, 1993).…”

Section: Introductionmentioning

confidence: 92%

Met-induced JNK activation is mediated by the adapter protein Crk and correlates with the Gab1 – Crk signaling complex formation

et al. 1999

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“…Activation of the Met tyrosine kinase by the TPR gene was originally described as a carcinogen-induced rearrangement in a human osteosarcoma cell line (Dean et al, 1987). The Tpr-Met fusion protein contains constitutively elevated Met tyrosine kinase activity and constitutes an ideal model to study the transforming activity of the Met kinase.…”

Section: Introductionmentioning

confidence: 99%

Oncogenic Met receptor induces ectopic structures in Xenopus embryos

Ishimura

et al. 2006

Oncogene

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When aberrantly expressed or activated, the Met receptor tyrosine kinase is involved in tumor invasiveness and metastasis. In this study, we have used the Xenopus embryonic system to define the role of various Met proximal-binding partners and downstream signaling pathways in regulating an induced morphogenetic event. We show that expression of an oncogenic derivative of the Met receptor (Tpr-Met) induces ectopic morphogenetic structures during Xenopus embryogenesis. Using variant forms of Tpr-Met that are engineered to recruit a specific signaling molecule of choice, we demonstrate that the sole recruitment of either the Grb2 or the Shc adaptor protein is sufficient to induce ectopic structures and anterior reduction, while the recruitment of PI-3Kinase (PI-3K) is necessary but not sufficient for this effect. In contrast, the recruitment of PLCc can initiate the induction, but fails to maintain or elongate supernumerary structures. Finally, evidence indicates that the Ras/Raf/MAPK pathway is necessary, but not sufficient to induce these structures. This study also emphasizes the importance of examining signaling molecules in the regulatory context that is provided by receptor/effector interactions when assessing a role in cell growth and differentiation.

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Characterization of the rearranged tpr-met oncogene breakpoint.

Cited by 45 publications

References 22 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

Met-induced JNK activation is mediated by the adapter protein Crk and correlates with the Gab1 – Crk signaling complex formation

Oncogenic Met receptor induces ectopic structures in Xenopus embryos

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