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Chromosome 12 origin in rings and giant markers in well-differentiated liposarcoma
Chromosome 12 Origin in Rings and Giant Markers in Well-Differentiated Liposarcoma
One of the principal types of liposarcoma (LPS) is the welldifferentiated LPS (WDLPS). WDLPS can grow to large size and, after excision, recur locally but almost never metastasize. In contrast to this low-grade malignant behavior, the cytogenetic features of WDLPS are quite dramatic and include supernumerary rings and giant marker chromosomes of undetermined origin (1-3). A case of WDLPS reported in your Journal by Stephenson et al. [3] in which the sole cytogenetic anomaly appeared to be addition of a giant marker chromosome to an otherwise normal diploid karyotype. Fluorescent in situ hybridization (FISH), using centromeric probes to chromosomes 1-4, 6-12, 16, 17, and X and a shared satellite probe to chromosome 1, 5, and 19 could not identify the origin of the giant marker. We have studied five cases of WDLPS, each with supernumerary ring or giant marker chromosomes and have used several FISH techniques to determine the origin of these remarkable chromosome rearrangements characteristic of WDLPS. We report results indicating that chromosome 12 may consistently be involved in formation of these rings and giant markers. The cytogenetics were performed by R- or G-banding of short-term cultured cells from each of the five tumor sampies. Three WDLPS samples had supernumerary rings, and two WDLPS samples had supernumerary giant marker chromosomes. The keryotype of these five cases (which correspond to our laboratory specimen numbers LPS1, 2, 91132, 91131, and 92295, respectively) are case 1, 48,XY, +2r/48, idem, 4p +; case 2, 47-50, X,-Y,i(8c0, + 1-3r; case 3, 47-50, XX, ÷ 1-4r; case 4, 47,XX, + mar; and case 5, 48,XY, + marl, + mar2, where M, M1, and M2 all represent giant marker chromosomes. The only detectable change in cases 3-5 was acquisition of a ring or giant rod. These cases provide strong evidence that the rings and rods may be key primary changes and that chromosome duplication is crucial to development of WDLPS. Our FISH studies so far have involved use of probes specific to the centromeres of 18 chromosomes and whole chromosome painting (WCP) probes specific to 11 chromosomes. The details concerning provenance, nature, use, and results with FISH will be reported when all studies are completed. The gist of the FISH analysis to date is that WCP shows clear involvement of chromosome 12 in formation of every ring and giant marker in these five cases of WDPLS. It is of interest that no signal from the centromere probe is specific to chromosome 12, and WCP indicates that at least five other chromosomes have played roles in the creation of these extraordinary rearrangements in WDLPS. © 1993 Elsevier Science Publishing Co., Inc. 655 Avenueof the Americas,New York, NY 10010
We are aware of the implications of chromosome 12 involvement in WDLPS. Another type of LPS, i.e., myx~id LPS, is characterized by a t(12; 16)(q13;pl 1) [4] and rearrangement of the transcription factor gene CHOP [5], and the 12q13 region harbors the SAS sequence and the MDM2 gene which are amplified in LPS [6, 7]. Thus, the knowledge that chromosome 12, almost surely 12q, is consistently involved in WDLPS adds a further element of complexity to the association between chromosome 12 and adipose tissue tumors. This work was supported by CNRS and grants from INSERM, the Associationpour la Recherchesur le Cancer, the F6d6mtionNationale des Centres de Lutte contre le Cancer, France. The authors thank Frederick Hecht for valuable editing help. FLORENCE PEDEUI~UR Laboratoire de G6n6tique Mol6culaire des Cancers Humains, URA CNRS 1462, Nice, France RON F. SUIJKERBUIJK Department of Human Genetics, JOSE VAN GAAL University Hospital, Nijmegen, WILLEMIJNVAN DE KLUNDERT The Netherlands JEAN-MICHELCOINDRE Laboratoired~natomopathologie, Fondation Bergoni~, Bordeaux, France ARBAINVAN HAELST
Departmentof Pathology, University Hospital, Nijmegen, The Netherlands
FRAN~OISE COLLIN Laboratoire d~natomopathologie, Centre Georges-Frangois Leclerc, Dijon, France KARIN HUFFERMANN Laboratoirede G6n6tique Mol6culaire CLAUDETURC-CAREL des Cancers Humains, URA CNRS 1462, Nice, France REFERENCES
1. Karakousis CP, Dal Cin P, Turc-Carel C, Limon J, Sandberg AA (1987): Chromosomal changes in soft-tissue sarcomas. A new diagnostic parameter. Arch Surg 122:1257-1260. 2. SreekantaiahC, Karakousis CP, Leong SPL, Sandberg AA (1992): Cytogenetic findings in liposercoma correlate with histopathologic subtypes. Cancer 69:2484-2495. 3. Stephenson CF, Barger CS, Leong SPL, Davis JR, Sandberg AA (1992): Analysis of a giant marker chromosome in a well-differentiated liposarcoma using cytogeneticsand fluorescence in situ hybridization. Cancer Genet Cytogenet 61:134-138. 4. Turc-Carel C, Limon J, Dal Cin P, Rao U, Karakousis C, Sandberg AA (1986): Cytogenetic studies of adipose tissue tumors. II. Recurrent reciprocal translocation t(12;16)(q13;p11) in myxoid liposarcomas. Cancer Genet Cytogenet 23:291-299. 5. Aman P, Ron D, Mandahl N, Fioretos T, Helm S, Arhaden C, Will6n H, Rydholm A, Mitelman F(1992): Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11). Genes Chrom Cancer 5:1-8. 133 Cancer Genet Cytogenet 66:133-134 (1993) 0165-4608/93/$06.00
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6. Meltzer PS, Jankowski SA, Dal Cin P, Sandberg AA, Paz B, Coccia MA (1991): Identification and cloning of a novel amplified sequence in human malignant fibrous histiocytoma derived from a region of chromosome 12 frequently rearranged in soft tissue tumors. Cell Growth Differ 2:495-501.
F. Pedeutour et al. 7. Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B (19921: Amplification of a gene encoding a p53.associated protein in human sarcomas. Nature 253:80-83.
One of the principal types of liposarcoma (LPS) is the welldifferentiated LPS (WDLPS). WDLPS can grow to large size and, after excision, recur locally but almost never metastasize. In contrast to this low-grade malignant behavior, the cytogenetic features of WDLPS are quite dramatic and include supernumerary rings and giant marker chromosomes of undetermined origin (1-3). A case of WDLPS reported in your Journal by Stephenson et al. [3] in which the sole cytogenetic anomaly appeared to be addition of a giant marker chromosome to an otherwise normal diploid karyotype. Fluorescent in situ hybridization (FISH), using centromeric probes to chromosomes 1-4, 6-12, 16, 17, and X and a shared satellite probe to chromosome 1, 5, and 19 could not identify the origin of the giant marker. We have studied five cases of WDLPS, each with supernumerary ring or giant marker chromosomes and have used several FISH techniques to determine the origin of these remarkable chromosome rearrangements characteristic of WDLPS. We report results indicating that chromosome 12 may consistently be involved in formation of these rings and giant markers. The cytogenetics were performed by R- or G-banding of short-term cultured cells from each of the five tumor sampies. Three WDLPS samples had supernumerary rings, and two WDLPS samples had supernumerary giant marker chromosomes. The keryotype of these five cases (which correspond to our laboratory specimen numbers LPS1, 2, 91132, 91131, and 92295, respectively) are case 1, 48,XY, +2r/48, idem, 4p +; case 2, 47-50, X,-Y,i(8c0, + 1-3r; case 3, 47-50, XX, ÷ 1-4r; case 4, 47,XX, + mar; and case 5, 48,XY, + marl, + mar2, where M, M1, and M2 all represent giant marker chromosomes. The only detectable change in cases 3-5 was acquisition of a ring or giant rod. These cases provide strong evidence that the rings and rods may be key primary changes and that chromosome duplication is crucial to development of WDLPS. Our FISH studies so far have involved use of probes specific to the centromeres of 18 chromosomes and whole chromosome painting (WCP) probes specific to 11 chromosomes. The details concerning provenance, nature, use, and results with FISH will be reported when all studies are completed. The gist of the FISH analysis to date is that WCP shows clear involvement of chromosome 12 in formation of every ring and giant marker in these five cases of WDPLS. It is of interest that no signal from the centromere probe is specific to chromosome 12, and WCP indicates that at least five other chromosomes have played roles in the creation of these extraordinary rearrangements in WDLPS. © 1993 Elsevier Science Publishing Co., Inc. 655 Avenueof the Americas,New York, NY 10010
We are aware of the implications of chromosome 12 involvement in WDLPS. Another type of LPS, i.e., myx~id LPS, is characterized by a t(12; 16)(q13;pl 1) [4] and rearrangement of the transcription factor gene CHOP [5], and the 12q13 region harbors the SAS sequence and the MDM2 gene which are amplified in LPS [6, 7]. Thus, the knowledge that chromosome 12, almost surely 12q, is consistently involved in WDLPS adds a further element of complexity to the association between chromosome 12 and adipose tissue tumors. This work was supported by CNRS and grants from INSERM, the Associationpour la Recherchesur le Cancer, the F6d6mtionNationale des Centres de Lutte contre le Cancer, France. The authors thank Frederick Hecht for valuable editing help. FLORENCE PEDEUI~UR Laboratoire de G6n6tique Mol6culaire des Cancers Humains, URA CNRS 1462, Nice, France RON F. SUIJKERBUIJK Department of Human Genetics, JOSE VAN GAAL University Hospital, Nijmegen, WILLEMIJNVAN DE KLUNDERT The Netherlands JEAN-MICHELCOINDRE Laboratoired~natomopathologie, Fondation Bergoni~, Bordeaux, France ARBAINVAN HAELST
Departmentof Pathology, University Hospital, Nijmegen, The Netherlands
FRAN~OISE COLLIN Laboratoire d~natomopathologie, Centre Georges-Frangois Leclerc, Dijon, France KARIN HUFFERMANN Laboratoirede G6n6tique Mol6culaire CLAUDETURC-CAREL des Cancers Humains, URA CNRS 1462, Nice, France REFERENCES
1. Karakousis CP, Dal Cin P, Turc-Carel C, Limon J, Sandberg AA (1987): Chromosomal changes in soft-tissue sarcomas. A new diagnostic parameter. Arch Surg 122:1257-1260. 2. SreekantaiahC, Karakousis CP, Leong SPL, Sandberg AA (1992): Cytogenetic findings in liposercoma correlate with histopathologic subtypes. Cancer 69:2484-2495. 3. Stephenson CF, Barger CS, Leong SPL, Davis JR, Sandberg AA (1992): Analysis of a giant marker chromosome in a well-differentiated liposarcoma using cytogeneticsand fluorescence in situ hybridization. Cancer Genet Cytogenet 61:134-138. 4. Turc-Carel C, Limon J, Dal Cin P, Rao U, Karakousis C, Sandberg AA (1986): Cytogenetic studies of adipose tissue tumors. II. Recurrent reciprocal translocation t(12;16)(q13;p11) in myxoid liposarcomas. Cancer Genet Cytogenet 23:291-299. 5. Aman P, Ron D, Mandahl N, Fioretos T, Helm S, Arhaden C, Will6n H, Rydholm A, Mitelman F(1992): Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11). Genes Chrom Cancer 5:1-8. 133 Cancer Genet Cytogenet 66:133-134 (1993) 0165-4608/93/$06.00
134
6. Meltzer PS, Jankowski SA, Dal Cin P, Sandberg AA, Paz B, Coccia MA (1991): Identification and cloning of a novel amplified sequence in human malignant fibrous histiocytoma derived from a region of chromosome 12 frequently rearranged in soft tissue tumors. Cell Growth Differ 2:495-501.
F. Pedeutour et al. 7. Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B (19921: Amplification of a gene encoding a p53.associated protein in human sarcomas. Nature 253:80-83.