Fusion of the EWS and CHOP genes in myxoid liposarcoma

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

“…22 Sequence analysis of this fragment revealed the fusion of exon 7 of the EWS gene with exon 2 of the CHOP gene, which was identical with the structure of the EWS-CHOP fusion gene found in five previously reported cases. 15,20,21 The structure of the longer fragment detected in the other two cases showed an in-frame fusion of exon 10 of the EWS gene to exon 2 of the CHOP gene ( Figure 2), which had not previously been reported (designated as a type 2 EWS-CHOP fusion gene in this report).…”

“…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][14][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.…”

Transforming activity of EWS/FLI is not strictly dependent upon DNA-binding activity

“…Taken together, these chromosomal translocations provide compelling genetic evidence that expression of one of several EWS/ETS chimeric proteins is a required event in the genesis of Ewing sarcoma. Related fusion proteins in which the RNA binding domains of EWS, or the related protein TLS/FUS, are replaced by DNA binding domains from di erent transcription factors have been identi®ed in four di erent types of human sarcoma in addition to Ewing sarcoma (Crozat et al, 1993;Labelle et al, 1995;Ladanyi and Gerald, 1994;Panagopoulos et al, 1996;Rabbitts et al, 1993;Zucman et al, 1993) and also in acute myeloid leukemia (Ichikawa et al, 1994).…”

SFT Thijsen et al. Hypersensitivity of bcr-abl progenitors to hyperthermia in patients with chronic myeloid leukemia

“…One reason for the apparent rarity of ETV6/ABL may be its complex origin, ie at least three chromosome breaks are necessary in order to generate a functional fusion because of the chromosomal orientation of these two genes. 5 This explanation is of course only valid if one adheres to the view that breakage and reunion underlying translocations are stochastic events, which is indirectly supported by the fact that other neoplasia-associated rearrangements requiring more than two breaks, such as t(10;11) in AML 7 and t(21;22) in Ewing sarcoma, 8 are also infrequent. Furthermore, Janssen et al 9 using RT-PCR, ascertained the incidence of ETV6/ABL in 216 patients with ALL without detecting a single case with this transcript, again emphasizing that this abnormality is indeed rare.…”