Fusion of an ETS‐family gene, EIAF, to EWS by t(17;22)(q12;q12) chromosome translocation in an undifferentiated sarcoma of infancy

Kaneko, Yasuhiko; Yoshida, Kôichi; Handa, Masafumi; Toyoda, Yasunori; Nishihira, Hirokazu; Tanaka, Yukichi; Sasaki, Yoshiro; Ishida, Setsuko; Higashino, Fumihiro; Fujinaga, Kei

doi:10.1002/(sici)1098-2264(199602)15:2<115::aid-gcc6>3.3.co;2-4

Cited by 71 publications

(89 citation statements)

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“…Chromosomal translocations involving the PEA3 gene have been implicated in sarcomas in humans (Kaneko et al, 1996). A segment of the EWS gene is translocated to the PEA3 gene (also known as E1A-F) in an undi erentiated sarcoma (Kaneko et al, 1996) and extraosseous Ewing's sarcoma (Urano et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

“…A segment of the EWS gene is translocated to the PEA3 gene (also known as E1A-F) in an undi erentiated sarcoma (Kaneko et al, 1996) and extraosseous Ewing's sarcoma (Urano et al, 1996). The same segment of EWS is translocated and juxtaposed to sequences encoding the ETS domain of other ets genes (Delattre et al, 1992;Zucman et al, 1993;Sorensen et al, 1994;Jeon et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer

et al. 1997

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HER2/Neu is overexpressed in 25 ± 30% of all human breast cancers as a result of both gene ampli®cation and enhanced transcription. Transcriptional upregulation of HER2/neu leads to a 6 ± 8-fold increased abundance of its mRNA per gene copy and likely results from the elevated activity of transcription factors acting on the HER2/neu promoter. Here we report that transcripts of PEA3, an ETS transcription factor implicated in oncogenesis, were increased in 93% of HER2/Neuoverexpressing human breast tumor samples. Analyses to uncover the molecular basis for elevated PEA3 transcripts in HER2/Neu-positive breast tumors revealed that the HER2/Neu receptor tyrosine kinase initiated an intracellular signaling cascade resulting in increased PEA3 transcriptional activity; transcriptionally-activated PEA3 stimulated HER2/neu and PEA3 gene transcription by binding to sites in the promoters of these genes. PEA3 also activates transcription of genes encoding matrix-degrading proteinases, enzymes required for tumor cell migration and invasion. These ®ndings implicate PEA3 in the initiation and progression of HER2/Neu positive breast cancer, and suggest that PEA3 and signaling proteins a ecting its regulation are appropriate therapeutic targets.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer

et al. 1997

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“…This site is roughly conserved in the other gene of the PEA3 group member involved in EWS translocation in Ewing's sarcoma, i.e. E1AF (Kaneko et al, 1996). As depicted in Figure 1, the consensus 3'-splice acceptor AG site is present in each intron characterized.…”

Section: Determination Of Human Etv1 Genomic Structurementioning

confidence: 93%

Characterization of the human and mouse ETV1/ER81 transcription factor genes: role of the two alternatively spliced isoforms in the human

Coutte

Monté

Imai³

et al. 1999

Oncogene

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The Ets transcription factors of the PEA3 group ± E1AF/PEA3, ETV1/ER81 and ERM ± are almost identical in the ETS DNA-binding and the transcriptional acidic domains. To accelerate our understanding of the molecular basis of putative diseases linked to ETV1 such as Ewing's sarcoma we characterized the human ETV1 and the mouse ER81 genes. We showed that these genes are both encoded by 13 exons in more than 90 kbp genomic DNA, and that the classical acceptor and donor splicing sites are present in each junction except for the 5' donor site of intron 9 where GT is replaced by TT. The genomic organization of the ETS and acidic domains in the human ETV1 and mouse ER81 (localized to chromosome 12) genes is similar to that observed in human ERM and human E1AF/PEA3 genes. Moreover, as in human ERM and human E1AF/ PEA3 genes, a ®rst untranslated exon is upstream from the ®rst methionine, and the mouse ER81 gene transcription is regulated by a 1.8 kbp of genomic DNA upstream from this exon. In human, the alternative splicing of the ETV1 gene leads to the presence (ETV1a) or the absence (ETV1b) of exon 5 encoding the Cterminal part of the transcriptional acidic domain, but without a ecting the alpha helix previously described as crucial for transactivation. We demonstrated here that the truncated isoform (human ETV1b) and the fulllength isoform (human ETV1a) bind similarly speci®c DNA Ets binding sites. Moreover, they both activate transcription similarly through the PKA-transduction pathway, so suggesting that this alternative splicing is not crucial for the function of this protein as a transcription factor. The comparison of human ETV1a and human ETV1b expression in the same tissues, such as the adrenal gland or the bladder, showed no clear-cut di erences. Altogether, these data open a new avenue of investigation leading to a better understanding of the functional role of this transcription factor.

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“…The diversity of fusion genes is most striking in Ewing's sarcoma. So far five different partners of the EWS gene have been reported, [2][3][4][5][6] and at least 12 different structures were found in the case of EWS-Fli1 fusion gene, 7,8 which is the most prevalent form of the fusion gene in Ewing's sarcoma. 8 In some tumors, the diversity seems to have biological significance, and several particular types of fusion genes were demonstrated to be associated with certain phenotypes such as prognosis or histological subtype.…”

Section: Fusion Genes Consisting Of Tls/fusmentioning

confidence: 99%

A Novel Type of EWS-CHOP Fusion Gene in Two Cases of Myxoid Liposarcoma

Hosaka

Nakashima

Kusuzaki

et al. 2002

The Journal of Molecular Diagnostics

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Fusion genes consisting of TLS/FUS and CHOP or EWS and CHOP are characteristic markers for myxoid/ round cell liposarcomas (MLS/RCLS). Several different structures of the fusion genes were reported in the case of the TLS/FUS-CHOP form, whereas only one type of structure has so far been found for the EWS-CHOP form, which consisted of exons 1 to 7 of the EWS and exons 2 to 4 of the CHOP gene. Here we describe a novel type of EWS-CHOP fusion gene in two cases of MLS/RCLS, which were found in a consecutive analysis of 21 cases. This fusion gene con- Tumor-specific fusion genes resulting from reciprocal chromosomal translocations have been detected in many bone and soft tissue tumors, and are now regarded as a major factor in the development of these tumors. 1 One of the common features of the fusion genes found in sarcomas is structural diversity, which is created by two factors: the component genes themselves, one is usually common and the other variable; and genomic breakpoints or alternative splicing in the components. The diversity of fusion genes is most striking in Ewing's sarcoma. So far five different partners of the EWS gene have been reported, 2-6 and at least 12 different structures were found in the case of EWS-Fli1 fusion gene, 7,8 which is the most prevalent form of the fusion gene in Ewing's sarcoma. 8 In some tumors, the diversity seems to have biological significance, and several particular types of fusion genes were demonstrated to be associated with certain phenotypes such as prognosis or histological subtype. 8 -12 In the case of MLS/RCLS, either the TLS/FUS (hereafter simply called TLS)-CHOP or EWS-CHOP fusion gene, the result of a t(12;16)(q13;p11) or a t(12;22)(q13;q12) translocation, respectively, 13-15 was found in almost all cases 16 -18 and the two are now considered a hallmark of this type of liposarcoma. Previous data indicated that the TLS-CHOP fusion gene was far more prevalent (95 to 98%) than the EWS-CHOP gene, 16 -18 having at least nine different structures due to breakpoints or alternative splicing. 19 On the other hand, only five cases of MLS/ RCLS harboring the EWS-CHOP fusion gene have been reported in the literature, all of which shared the same structure consisting of exons 1 to 7 of the EWS gene and exons 2 to 4 of the CHOP gene (designated as the type 1 EWS-CHOP fusion gene in this report). 15,20,21 No definite correlation has been reported between any particular type of TLS-CHOP or EWS-CHOP fusion gene and the clinicopathological features of MLS/RCLS. In this report, we describe the results of fusion gene analyses of 21 cases of MLS/RCLS, in which we found a novel type of EWS-CHOP fusion gene in two cases. Materials and Methods Tumor Samples and Nucleic Acid ExtractionTwenty-one cases of MLS/RCLS were examined in this study, 13 of which were used previously in breakpoint analyses of the TLS-CHOP fusion gene. 22,23 Clinical and

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Fusion of an ETS‐family gene, EIAF, to EWS by t(17;22)(q12;q12) chromosome translocation in an undifferentiated sarcoma of infancy

Cited by 71 publications

References 0 publications

HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer

HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer

Characterization of the human and mouse ETV1/ER81 transcription factor genes: role of the two alternatively spliced isoforms in the human

A Novel Type of EWS-CHOP Fusion Gene in Two Cases of Myxoid Liposarcoma

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