G2Cdb::Human Disease report

Disease id
D00000009
Name
Myxoid liposarcoma
Nervous system disease
no

Genes (1)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00002162 FUS
fused in sarcoma
Y (7485386) Translocation fusion (with another gene) (TF) Y
G00002162 FUS
fused in sarcoma
Y (7566973) Translocation fusion (with another gene) (TF) Y
G00002162 FUS
fused in sarcoma
Y (7805034) Translocation fusion (with another gene) (TF) Y
G00002162 FUS
fused in sarcoma
Y (7987849) Translocation fusion (with another gene) (TF) Y
G00002162 FUS
fused in sarcoma
Y (8523819) Translocation fusion (with another gene) (TF) Y
G00002162 FUS
fused in sarcoma
Y (9315104) Translocation fusion (with another gene) (TF) Y
G00002162 FUS
fused in sarcoma
Y (9676855) Translocation fusion (with another gene) (TF) Y
G00002162 FUS
fused in sarcoma
Y (10347549) Translocation fusion (with another gene) (TF) Y
G00002162 FUS
fused in sarcoma
Y (11162437) Translocation fusion (with another gene) (TF) Y

References

  • A novel FUS/CHOP chimera in myxoid liposarcoma.

    Panagopoulos I, Mertens F, Isaksson M and Mandahl N

    Department of Clinical Genetics, Lund University Hospital, Lund, S-221 85, Sweden. ioannis.panagopoulos@klingen.lu.se

    The cytogenetic hallmark of myxoid liposarcoma is the chromosomal aberration t(12;16)(q13;p11), which is pathognomonic for this tumor type. The translocation results in the hybrid gene FUS/CHOP, where the central and C-terminal parts of FUS, coding for the RNA binding domain and the RGG triplet motif, are replaced by the full length CHOP protein. Thus, CHOP is under the control of the FUS promoter and the FUS/CHOP chimera contains the 5'-terminal part of FUS which provides a transcriptional activation function. Although different structural variations of the FUS/CHOP chimeric transcript have been reported, none of them contains the parts of FUS encoding the RNA binding properties. An explanation is the location of the genomic breakpoint in FUS, which frequently occurs in the region spanning exon 5 to intron 8. We describe here a case of myxoid liposarcoma containing two novel FUS/CHOP chimeric transcripts and with the breakpoint occurring in intron 14 of FUS. Reverse transcription-polymerase chain reaction, using FUS forward and CHOP reverse primers, amplified strongly a 2.1-kbp DNA fragment and weakly a 0.9-kbp DNA fragment. Direct sequencing showed that in the 2.1-kbp transcript nt 1474, which corresponds to the third nucleotide of exon 14 of FUS, was in-frame fused to exon 2 of CHOP. In the 0.9-kbp DNA fragment, exon 3 of FUS was in-frame fused to exon 2 of CHOP. Genomic analyses revealed that the breaks were located at the end of exon 14/beginning of intron 14 of FUS and in intron 1 of CHOP and that microdeletions had occurred in the close vicinity of the breakpoints.

    Biochemical and biophysical research communications 2000;279;3;838-45

  • A rare chimeric TLS/FUS-CHOP transcript in a patient with multiple liposarcomas: a case report.

    Schneider-Stock R, Rys J, Walter H, Limon J, Iliszko M, Niezabitowski A and Roessner A

    Department of Pathology, Otto-von-Guericke University, Magdeburg, Germany.

    Myxoid liposarcomas harbor a unique and specific t(12;16)(q13,p11) chromosomal translocation. The breakpoint has recently been identified, and involvement of the TLS/FUS gene on chromosome 16 and the CHOP gene on chromosome 12 was demonstrated. We report a case of a 45-year-old woman who developed multiple malignant lipomatous tumors of unknown origin and myxoid/round cell histology at different locations. To examine the diagnostic potential of this translocation and to develop a hypothesis on the origin of the tumors, we used cytogenetic and molecular cytogenetic methods (reverse transcription polymerase chain reaction, RT-PCR). We identified a chimeric RNA transcript in the second recurrence in the thigh/groin, as well as in another tumor in the mediastinum, which has an additional sequence of 33 bp, known as fusion transcript type III. Cytogenetic analysis of another tumor in retroperitoneal space revealed a rare type of unbalanced translocation der(16)t(12;16). We hypothesize that these tumors are metastases rather than multicentric tumors. The detection of the chimeric message in the present case is not only useful for differential diagnosis, but also for analyzing the origin of multiple neoplasms.

    Cancer genetics and cytogenetics 1999;111;2;130-3

  • Analysis of FUS-CHOP fusion transcripts in different types of soft tissue liposarcoma and their diagnostic implications.

    Willeke F, Ridder R, Mechtersheimer G, Schwarzbach M, Duwe A, Weitz J, Lehnert T, Herfarth C and von Knebel Doeberitz M

    Department of Surgery, University of Heidelberg, Germany. frank_willeke@ukl.uni-heidelberg.de

    In myxoid and round cell liposarcomas, a specific chromosomal translocation [(12;16)(q13;p11)] results in the expression of chimeric fusion transcripts encompassing parts of the FUS gene (16p11) at their 5' ends and the CHOP gene (12q13) at their 3' ends. Using a reverse transcription-PCR protocol, we determined the prevalence of FUS-CHOP fusion transcripts in a series of liposarcoma samples. Fusion transcripts were detected in 13 of 30 biopsy samples from soft tissue liposarcomas. Expression of fusion transcripts was not restricted to myxoid and round cell liposarcomas, as suggested previously; it was also detected in 1 of 3 well-differentiated and 4 of 14 pleomorphic liposarcomas. Sequence analysis revealed four different FUS-CHOP fusion transcript variants, two of which have not been described before. Furthermore, using FUS-CHOP fusion transcripts as targets in reverse transcription-PCR assays, we detected disseminated tumor cells in peripheral blood or bone marrow in 3 of 5 patients undergoing surgery for soft tissue liposarcoma.

    Clinical cancer research : an official journal of the American Association for Cancer Research 1998;4;7;1779-84

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

    Panagopoulos I, Lassen C, Isaksson M, Mitelman F, Mandahl N and Aman P

    Department of Clinical Genetics, Lund University Hospital, Sweden.

    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 TC-dinucleotide repeat region and a sequence similar to the chi bacterial recombination element was found to flank 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 specific recognition sites for DNA-binding proteins and have functional importance in the recombination events taking place between the chromosomes. Different sequence motifs may, however, play a role in each individual case.

    Oncogene 1997;15;11;1357-62

  • FUS/TLS-CHOP chimeric transcripts in liposarcoma tissues.

    Yang X, Nagasaki K, Egawa S, Maruyama K, Futami H, Tsukada T, Yokoyama R, Beppu Y, Fukuma H, Shimoda T et al.

    Growth Factor Division, National Cancer Center Research Institute, Tokyo.

    Myxoid liposarcoma and malignant fibrous histiocytoma (MFH) are common soft tissue sarcomas of adulthood. Histopathologically they often show intratumor heterogeneity. In some cases, differential diagnosis of liposarcoma and MFH is difficult. It has been reported that myxoid liposarcomas are characterized by chromosomal translocation t (12; 16) (q13; p11), and that this results in two types (type I and type II) of FUS/TLS-CHOP fusion transcripts. In this study, the FUS/TLS-CHOP chimeric transcripts in seven malignant soft tissue tumors of Asian patients were analyzed by reverse transcription-polymerase chain reaction, DNA blot hybridization and nucleotide sequencing. One myxoid liposarcoma and two round cell liposarcomas possessed a chimeric transcript whose fusion point was the same as that of the type I fusion transcript reported previously for myxoid liposarcoma. We were thus able to detect the type I FUS/TLS-CHOP fusion transcript in clinical specimens of liposarcoma from Asian patients, including the first examples of round cell liposarcoma. These results suggest that the detection of FUS/TLS-CHOP chimeric transcripts or chimeric genes can be used as a diagnostic tool for the pathological diagnosis of liposarcomas.

    Japanese journal of clinical oncology 1995;25;6;234-9

  • Chimeric TLS/FUS-CHOP gene expression and the heterogeneity of its junction in human myxoid and round cell liposarcoma.

    Kuroda M, Ishida T, Horiuchi H, Kida N, Uozaki H, Takeuchi H, Tsuji K, Imamura T, Mori S, Machinami R et al.

    Department of Pathology, University of Tokyo, Japan.

    Myxoid liposarcomas have a unique and specific t(12;16)q13;p11) chromosomal translocation. The breakpoint has recently been identified and shown to involve the TLS/FUS gene on chromosome 16 and the CHOP gene on chromosome 12. This translocation causes fusion of these genes resulting in the expression of a novel chimeric TLS/FUS-CHOP message. Using the polymerase chain reaction with primer sets derived from sequences of TLS/FUS and CHOP cDNAs, we could amplify three types of the fusion transcripts from seven of seven samples of myxoid and round cell liposarcomas. In six of the seven positive samples, two kinds of chimeric messenger RNAs were found that have been reported previously. However, the last sample had a novel chimeric message that had an extra sequence of 33 bp derived from the TLS/FUS gene. Thus, it was shown that these fusion transcripts had a varying extent of the sequence of TLS/FUS gene incorporated at the site of the fusion. However, the TLS/FUS-CHOP fusion transcripts were not detected in two pleomorphic liposarcomas or in three myxoid variants of malignant fibrous histiocytomas. Our findings indicate that in liposarcomas TLS/FUS-CHOP fusion transcripts have variations at the junction of chimeric messages, which was the case for Ewing's sarcoma. Detection of the chimeric message by reverse transcription polymerase chain reaction was also suggested to be a useful approach for the diagnosis of myxoid and round cell liposarcomas that have (12;16) translocation, and for distinguishing them from pleomorphic liposarcoma and myxoid variant of malignant fibrous histiocytomas.

    The American journal of pathology 1995;147;5;1221-7

  • Two distinct FUS breakpoint clusters in myxoid liposarcoma and acute myeloid leukemia with the translocations t(12;16) and t(16;21).

    Panagopoulos I, Mandahl N, Mitelman F and Aman P

    Department of Clinical Genetics, Lund University Hospital, Sweden.

    The FUS gene, which maps to 16p11, is fused to the CHOP gene in the t(12;16) (q13;p11) that characterizes myxoid liposarcomas (MLS) and to the ERG gene in acute myeloid leukemia (AML) with t(16;21) (p11;q22). In the present study we have mapped the breakpoints within FUS in 13 MLS with t(12;16) and in one AML with t(16;21). This region of FUS is about 3.9 kb and contains four exons. The breakpoints clustered to two zones (1 and 2). A strong association was found between the two known types of FUS/CHOP transcripts and the genomic localization of the breakpoints. In all cases expressing only type I or both type I and II FUS/CHOP transcript the genomic breakpoints mapped to zone 1. In all cases expressing only the type II transcript the breakpoints occurred in zone 2. The breakpoint in the AML case was in zone 1, suggesting that in-frame fusion transcripts are selected by similar mechanisms in both MLS and AML.

    Oncogene 1995;11;6;1133-7

  • Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: molecular and cytogenetic analysis.

    Knight JC, Renwick PJ, Dal Cin P, Van den Berghe H and Fletcher CD

    Department of Histopathology, U.M.D.S. St. Thomas' Hospital, London, United Kingdom.

    Translocation t(12;16)(q13;p11) is regarded as a diagnostic marker for myxoid liposarcoma. Cytogenetic data on round cell liposarcomas and combined myxoid and round cell tumors is scarce, and the genetic basis of progression of myxoid tumors to high grade, round cell lesions is unknown. We have accumulated six round cell, four combined myxoid and round cell, and three myxoid liposarcomas for analysis. t(12;16)(q13;p11) was present in three round cell lesions and was detectable in all of the tumors by DNA analysis. In each tumor type, the CHOP gene in 12q13 was rearranged and fused to the TLS gene in 16p11. A variant TLS-CHOP RNA transcript was detected by polymerase chain reaction but did not correlate with clinicopathological data. No distinguishing cytogenetic or molecular markers for round cell or mixed lesions were found. The histogenic and genetic relatedness of myxoid and round cell liposarcomas is apparent from these data.

    Cancer research 1995;55;1;24-7

  • Characterization of the CHOP breakpoints and fusion transcripts in myxoid liposarcomas with the 12;16 translocation.

    Panagopoulos I, Mandahl N, Ron D, Höglund M, Nilbert M, Mertens F, Mitelman F and Aman P

    Department of Clinical Genetics, Lund University Hospital, Sweden.

    Myxoid liposarcomas are cytogenetically characterized by t(12;16)(q13;p11). The translocation results in rearrangements of the CHOP gene in 12q13 and the FUS gene in 16p11, creating a fusion gene where the RNA-binding domain of FUS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. In the present study, we have mapped 16 genomic breakpoints in the region of the CHOP gene and isolated and sequenced a new variant (type II) of the chimeric FUS/CHOP transcript. The genomic breakpoints were dispersed along a 7.50-kilobase pair region from a SstI cleavage site upstream of the promoter of CHOP to a PstI cleavage site within intron 1. Reverse transcriptase-polymerase chain reaction analysis of tumor samples demonstrated the presence of two variant fragments, 654 base pairs (type I) and 378 base pairs (type II) in size. Of the 13 samples analyzed, 7 showed the smaller, 3 showed the larger, and 3 showed both types of transcripts. We cloned and sequenced the two fragments and found in type II a novel fusion point in the FUS mRNA 275 base pairs upstream of that present in the type I transcript. In both types of transcripts the interrupted FUS is followed by the entire exon 2 of CHOP. As a consequence the normally nontranslated exon 2 is translated and in both types there is in the junction between FUS and CHOP a shift from a FUS glycine codon to a valine codon in the chimeric mRNA.

    Funded by: NCI NIH HHS: CA60945

    Cancer research 1994;54;24;6500-3

Literature (9)

Pubmed - human_disease

  • A novel FUS/CHOP chimera in myxoid liposarcoma.

    Panagopoulos I, Mertens F, Isaksson M and Mandahl N

    Department of Clinical Genetics, Lund University Hospital, Lund, S-221 85, Sweden. ioannis.panagopoulos@klingen.lu.se

    The cytogenetic hallmark of myxoid liposarcoma is the chromosomal aberration t(12;16)(q13;p11), which is pathognomonic for this tumor type. The translocation results in the hybrid gene FUS/CHOP, where the central and C-terminal parts of FUS, coding for the RNA binding domain and the RGG triplet motif, are replaced by the full length CHOP protein. Thus, CHOP is under the control of the FUS promoter and the FUS/CHOP chimera contains the 5'-terminal part of FUS which provides a transcriptional activation function. Although different structural variations of the FUS/CHOP chimeric transcript have been reported, none of them contains the parts of FUS encoding the RNA binding properties. An explanation is the location of the genomic breakpoint in FUS, which frequently occurs in the region spanning exon 5 to intron 8. We describe here a case of myxoid liposarcoma containing two novel FUS/CHOP chimeric transcripts and with the breakpoint occurring in intron 14 of FUS. Reverse transcription-polymerase chain reaction, using FUS forward and CHOP reverse primers, amplified strongly a 2.1-kbp DNA fragment and weakly a 0.9-kbp DNA fragment. Direct sequencing showed that in the 2.1-kbp transcript nt 1474, which corresponds to the third nucleotide of exon 14 of FUS, was in-frame fused to exon 2 of CHOP. In the 0.9-kbp DNA fragment, exon 3 of FUS was in-frame fused to exon 2 of CHOP. Genomic analyses revealed that the breaks were located at the end of exon 14/beginning of intron 14 of FUS and in intron 1 of CHOP and that microdeletions had occurred in the close vicinity of the breakpoints.

    Biochemical and biophysical research communications 2000;279;3;838-45

  • A rare chimeric TLS/FUS-CHOP transcript in a patient with multiple liposarcomas: a case report.

    Schneider-Stock R, Rys J, Walter H, Limon J, Iliszko M, Niezabitowski A and Roessner A

    Department of Pathology, Otto-von-Guericke University, Magdeburg, Germany.

    Myxoid liposarcomas harbor a unique and specific t(12;16)(q13,p11) chromosomal translocation. The breakpoint has recently been identified, and involvement of the TLS/FUS gene on chromosome 16 and the CHOP gene on chromosome 12 was demonstrated. We report a case of a 45-year-old woman who developed multiple malignant lipomatous tumors of unknown origin and myxoid/round cell histology at different locations. To examine the diagnostic potential of this translocation and to develop a hypothesis on the origin of the tumors, we used cytogenetic and molecular cytogenetic methods (reverse transcription polymerase chain reaction, RT-PCR). We identified a chimeric RNA transcript in the second recurrence in the thigh/groin, as well as in another tumor in the mediastinum, which has an additional sequence of 33 bp, known as fusion transcript type III. Cytogenetic analysis of another tumor in retroperitoneal space revealed a rare type of unbalanced translocation der(16)t(12;16). We hypothesize that these tumors are metastases rather than multicentric tumors. The detection of the chimeric message in the present case is not only useful for differential diagnosis, but also for analyzing the origin of multiple neoplasms.

    Cancer genetics and cytogenetics 1999;111;2;130-3

  • Analysis of FUS-CHOP fusion transcripts in different types of soft tissue liposarcoma and their diagnostic implications.

    Willeke F, Ridder R, Mechtersheimer G, Schwarzbach M, Duwe A, Weitz J, Lehnert T, Herfarth C and von Knebel Doeberitz M

    Department of Surgery, University of Heidelberg, Germany. frank_willeke@ukl.uni-heidelberg.de

    In myxoid and round cell liposarcomas, a specific chromosomal translocation [(12;16)(q13;p11)] results in the expression of chimeric fusion transcripts encompassing parts of the FUS gene (16p11) at their 5' ends and the CHOP gene (12q13) at their 3' ends. Using a reverse transcription-PCR protocol, we determined the prevalence of FUS-CHOP fusion transcripts in a series of liposarcoma samples. Fusion transcripts were detected in 13 of 30 biopsy samples from soft tissue liposarcomas. Expression of fusion transcripts was not restricted to myxoid and round cell liposarcomas, as suggested previously; it was also detected in 1 of 3 well-differentiated and 4 of 14 pleomorphic liposarcomas. Sequence analysis revealed four different FUS-CHOP fusion transcript variants, two of which have not been described before. Furthermore, using FUS-CHOP fusion transcripts as targets in reverse transcription-PCR assays, we detected disseminated tumor cells in peripheral blood or bone marrow in 3 of 5 patients undergoing surgery for soft tissue liposarcoma.

    Clinical cancer research : an official journal of the American Association for Cancer Research 1998;4;7;1779-84

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

    Panagopoulos I, Lassen C, Isaksson M, Mitelman F, Mandahl N and Aman P

    Department of Clinical Genetics, Lund University Hospital, Sweden.

    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 TC-dinucleotide repeat region and a sequence similar to the chi bacterial recombination element was found to flank 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 specific recognition sites for DNA-binding proteins and have functional importance in the recombination events taking place between the chromosomes. Different sequence motifs may, however, play a role in each individual case.

    Oncogene 1997;15;11;1357-62

  • FUS/TLS-CHOP chimeric transcripts in liposarcoma tissues.

    Yang X, Nagasaki K, Egawa S, Maruyama K, Futami H, Tsukada T, Yokoyama R, Beppu Y, Fukuma H, Shimoda T et al.

    Growth Factor Division, National Cancer Center Research Institute, Tokyo.

    Myxoid liposarcoma and malignant fibrous histiocytoma (MFH) are common soft tissue sarcomas of adulthood. Histopathologically they often show intratumor heterogeneity. In some cases, differential diagnosis of liposarcoma and MFH is difficult. It has been reported that myxoid liposarcomas are characterized by chromosomal translocation t (12; 16) (q13; p11), and that this results in two types (type I and type II) of FUS/TLS-CHOP fusion transcripts. In this study, the FUS/TLS-CHOP chimeric transcripts in seven malignant soft tissue tumors of Asian patients were analyzed by reverse transcription-polymerase chain reaction, DNA blot hybridization and nucleotide sequencing. One myxoid liposarcoma and two round cell liposarcomas possessed a chimeric transcript whose fusion point was the same as that of the type I fusion transcript reported previously for myxoid liposarcoma. We were thus able to detect the type I FUS/TLS-CHOP fusion transcript in clinical specimens of liposarcoma from Asian patients, including the first examples of round cell liposarcoma. These results suggest that the detection of FUS/TLS-CHOP chimeric transcripts or chimeric genes can be used as a diagnostic tool for the pathological diagnosis of liposarcomas.

    Japanese journal of clinical oncology 1995;25;6;234-9

  • Chimeric TLS/FUS-CHOP gene expression and the heterogeneity of its junction in human myxoid and round cell liposarcoma.

    Kuroda M, Ishida T, Horiuchi H, Kida N, Uozaki H, Takeuchi H, Tsuji K, Imamura T, Mori S, Machinami R et al.

    Department of Pathology, University of Tokyo, Japan.

    Myxoid liposarcomas have a unique and specific t(12;16)q13;p11) chromosomal translocation. The breakpoint has recently been identified and shown to involve the TLS/FUS gene on chromosome 16 and the CHOP gene on chromosome 12. This translocation causes fusion of these genes resulting in the expression of a novel chimeric TLS/FUS-CHOP message. Using the polymerase chain reaction with primer sets derived from sequences of TLS/FUS and CHOP cDNAs, we could amplify three types of the fusion transcripts from seven of seven samples of myxoid and round cell liposarcomas. In six of the seven positive samples, two kinds of chimeric messenger RNAs were found that have been reported previously. However, the last sample had a novel chimeric message that had an extra sequence of 33 bp derived from the TLS/FUS gene. Thus, it was shown that these fusion transcripts had a varying extent of the sequence of TLS/FUS gene incorporated at the site of the fusion. However, the TLS/FUS-CHOP fusion transcripts were not detected in two pleomorphic liposarcomas or in three myxoid variants of malignant fibrous histiocytomas. Our findings indicate that in liposarcomas TLS/FUS-CHOP fusion transcripts have variations at the junction of chimeric messages, which was the case for Ewing's sarcoma. Detection of the chimeric message by reverse transcription polymerase chain reaction was also suggested to be a useful approach for the diagnosis of myxoid and round cell liposarcomas that have (12;16) translocation, and for distinguishing them from pleomorphic liposarcoma and myxoid variant of malignant fibrous histiocytomas.

    The American journal of pathology 1995;147;5;1221-7

  • Two distinct FUS breakpoint clusters in myxoid liposarcoma and acute myeloid leukemia with the translocations t(12;16) and t(16;21).

    Panagopoulos I, Mandahl N, Mitelman F and Aman P

    Department of Clinical Genetics, Lund University Hospital, Sweden.

    The FUS gene, which maps to 16p11, is fused to the CHOP gene in the t(12;16) (q13;p11) that characterizes myxoid liposarcomas (MLS) and to the ERG gene in acute myeloid leukemia (AML) with t(16;21) (p11;q22). In the present study we have mapped the breakpoints within FUS in 13 MLS with t(12;16) and in one AML with t(16;21). This region of FUS is about 3.9 kb and contains four exons. The breakpoints clustered to two zones (1 and 2). A strong association was found between the two known types of FUS/CHOP transcripts and the genomic localization of the breakpoints. In all cases expressing only type I or both type I and II FUS/CHOP transcript the genomic breakpoints mapped to zone 1. In all cases expressing only the type II transcript the breakpoints occurred in zone 2. The breakpoint in the AML case was in zone 1, suggesting that in-frame fusion transcripts are selected by similar mechanisms in both MLS and AML.

    Oncogene 1995;11;6;1133-7

  • Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: molecular and cytogenetic analysis.

    Knight JC, Renwick PJ, Dal Cin P, Van den Berghe H and Fletcher CD

    Department of Histopathology, U.M.D.S. St. Thomas' Hospital, London, United Kingdom.

    Translocation t(12;16)(q13;p11) is regarded as a diagnostic marker for myxoid liposarcoma. Cytogenetic data on round cell liposarcomas and combined myxoid and round cell tumors is scarce, and the genetic basis of progression of myxoid tumors to high grade, round cell lesions is unknown. We have accumulated six round cell, four combined myxoid and round cell, and three myxoid liposarcomas for analysis. t(12;16)(q13;p11) was present in three round cell lesions and was detectable in all of the tumors by DNA analysis. In each tumor type, the CHOP gene in 12q13 was rearranged and fused to the TLS gene in 16p11. A variant TLS-CHOP RNA transcript was detected by polymerase chain reaction but did not correlate with clinicopathological data. No distinguishing cytogenetic or molecular markers for round cell or mixed lesions were found. The histogenic and genetic relatedness of myxoid and round cell liposarcomas is apparent from these data.

    Cancer research 1995;55;1;24-7

Pubmed - other

  • Characterization of the CHOP breakpoints and fusion transcripts in myxoid liposarcomas with the 12;16 translocation.

    Panagopoulos I, Mandahl N, Ron D, Höglund M, Nilbert M, Mertens F, Mitelman F and Aman P

    Department of Clinical Genetics, Lund University Hospital, Sweden.

    Myxoid liposarcomas are cytogenetically characterized by t(12;16)(q13;p11). The translocation results in rearrangements of the CHOP gene in 12q13 and the FUS gene in 16p11, creating a fusion gene where the RNA-binding domain of FUS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. In the present study, we have mapped 16 genomic breakpoints in the region of the CHOP gene and isolated and sequenced a new variant (type II) of the chimeric FUS/CHOP transcript. The genomic breakpoints were dispersed along a 7.50-kilobase pair region from a SstI cleavage site upstream of the promoter of CHOP to a PstI cleavage site within intron 1. Reverse transcriptase-polymerase chain reaction analysis of tumor samples demonstrated the presence of two variant fragments, 654 base pairs (type I) and 378 base pairs (type II) in size. Of the 13 samples analyzed, 7 showed the smaller, 3 showed the larger, and 3 showed both types of transcripts. We cloned and sequenced the two fragments and found in type II a novel fusion point in the FUS mRNA 275 base pairs upstream of that present in the type I transcript. In both types of transcripts the interrupted FUS is followed by the entire exon 2 of CHOP. As a consequence the normally nontranslated exon 2 is translated and in both types there is in the junction between FUS and CHOP a shift from a FUS glycine codon to a valine codon in the chimeric mRNA.

    Funded by: NCI NIH HHS: CA60945

    Cancer research 1994;54;24;6500-3

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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