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British Journal of Cancer logoLink to British Journal of Cancer
. 1997;75(10):1403–1409. doi: 10.1038/bjc.1997.242

Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization.

G Armengol 1, M Tarkkanen 1, M Virolainen 1, A Forus 1, J Valle 1, T Böhling 1, S Asko-Seljavaara 1, C Blomqvist 1, I Elomaa 1, E Karaharju 1, A H Kivioja 1, M A Siimes 1, E Tukiainen 1, M R Caballín 1, O Myklebost 1, S Knuutila 1
PMCID: PMC2223493  PMID: 9166930

Abstract

Comparative genomic hybridization (CGH) was used to detect copy number changes of DNA sequences in the Ewing family of tumours (ET). We analysed 20 samples from 17 patients. Fifteen tumours (75%) showed copy number changes. Gains of DNA sequences were much more frequent than losses, the majority of the gains affecting whole chromosomes or whole chromosome arms. Recurrent findings included copy number increases for chromosomes 8 (seven out of 20 samples; 35%), 1q (five samples; 25%) and 12 (five samples; 25%). The minimal common regions of these gains were the whole chromosomes 8 and 12, and 1q21-22. High-level amplifications affected 8q13-24, 1q and 1q21-22, each once. Southern blot analysis of the specimen with high-level amplification at 1q21-22 showed an amplification of FLG and SPRR3, both mapped to this region. All cases with a gain of chromosome 12 simultaneously showed a gain of chromosome 8. Comparison of CGH findings with cytogenetic analysis of the same tumours and previous cytogenetic reports of ET showed, in general, concordant results. In conclusion, our findings confirm that secondary changes, which may have prognostic significance in ET, are trisomy 8, trisomy 12 and a gain of DNA sequences in 1q.

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Selected References

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  1. Ambros I. M., Ambros P. F., Strehl S., Kovar H., Gadner H., Salzer-Kuntschik M. MIC2 is a specific marker for Ewing's sarcoma and peripheral primitive neuroectodermal tumors. Evidence for a common histogenesis of Ewing's sarcoma and peripheral primitive neuroectodermal tumors from MIC2 expression and specific chromosome aberration. Cancer. 1991 Apr 1;67(7):1886–1893. doi: 10.1002/1097-0142(19910401)67:7<1886::aid-cncr2820670712>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  2. Delattre O., Zucman J., Plougastel B., Desmaze C., Melot T., Peter M., Kovar H., Joubert I., de Jong P., Rouleau G. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature. 1992 Sep 10;359(6391):162–165. doi: 10.1038/359162a0. [DOI] [PubMed] [Google Scholar]
  3. Douglass E. C., Rowe S. T., Valentine M., Parham D., Meyer W. H., Thompson E. I. A second nonrandom translocation, der(16)t(1;16)(q21;q13), in Ewing sarcoma and peripheral neuroectodermal tumor. Cytogenet Cell Genet. 1990;53(2-3):87–90. doi: 10.1159/000132901. [DOI] [PubMed] [Google Scholar]
  4. Engelkamp D., Schäfer B. W., Mattei M. G., Erne P., Heizmann C. W. Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6547–6551. doi: 10.1073/pnas.90.14.6547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Forus A., Flørenes V. A., Maelandsmo G. M., Meltzer P. S., Fodstad O., Myklebost O. Mapping of amplification units in the q13-14 region of chromosome 12 in human sarcomas: some amplica do not include MDM2. Cell Growth Differ. 1993 Dec;4(12):1065–1070. [PubMed] [Google Scholar]
  6. Forus A., Weghuis D. O., Smeets D., Fodstad O., Myklebost O., Geurts van Kessel A. Comparative genomic hybridization analysis of human sarcomas: II. Identification of novel amplicons at 6p and 17p in osteosarcomas. Genes Chromosomes Cancer. 1995 Sep;14(1):15–21. doi: 10.1002/gcc.2870140104. [DOI] [PubMed] [Google Scholar]
  7. Forus A., Weghuis D. O., Smeets D., Fodstad O., Myklebost O., van Kessel A. G. Comparative genomic hybridization analysis of human sarcomas: I. Occurrence of genomic imbalances and identification of a novel major amplicon at 1q21-q22 in soft tissue sarcomas. Genes Chromosomes Cancer. 1995 Sep;14(1):8–14. doi: 10.1002/gcc.2870140103. [DOI] [PubMed] [Google Scholar]
  8. Gibbs S., Fijneman R., Wiegant J., van Kessel A. G., van De Putte P., Backendorf C. Molecular characterization and evolution of the SPRR family of keratinocyte differentiation markers encoding small proline-rich proteins. Genomics. 1993 Jun;16(3):630–637. doi: 10.1006/geno.1993.1240. [DOI] [PubMed] [Google Scholar]
  9. Hohl D., de Viragh P. A., Amiguet-Barras F., Gibbs S., Backendorf C., Huber M. The small proline-rich proteins constitute a multigene family of differentially regulated cornified cell envelope precursor proteins. J Invest Dermatol. 1995 Jun;104(6):902–909. doi: 10.1111/1523-1747.ep12606176. [DOI] [PubMed] [Google Scholar]
  10. Huang L. S., Bock S. C., Feinstein S. I., Breslow J. L. Human apolipoprotein B cDNA clone isolation and demonstration that liver apolipoprotein B mRNA is 22 kilobases in length. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6825–6829. doi: 10.1073/pnas.82.20.6825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jeon I. S., Davis J. N., Braun B. S., Sublett J. E., Roussel M. F., Denny C. T., Shapiro D. N. A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene. 1995 Mar 16;10(6):1229–1234. [PubMed] [Google Scholar]
  12. Kallioniemi A., Kallioniemi O. P., Sudar D., Rutovitz D., Gray J. W., Waldman F., Pinkel D. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science. 1992 Oct 30;258(5083):818–821. doi: 10.1126/science.1359641. [DOI] [PubMed] [Google Scholar]
  13. Kallioniemi O. P., Kallioniemi A., Piper J., Isola J., Waldman F. M., Gray J. W., Pinkel D. Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors. Genes Chromosomes Cancer. 1994 Aug;10(4):231–243. doi: 10.1002/gcc.2870100403. [DOI] [PubMed] [Google Scholar]
  14. Ladanyi M., Lewis R., Jhanwar S. C., Gerald W., Huvos A. G., Healey J. H. MDM2 and CDK4 gene amplification in Ewing's sarcoma. J Pathol. 1995 Feb;175(2):211–217. doi: 10.1002/path.1711750209. [DOI] [PubMed] [Google Scholar]
  15. McKeon C., Thiele C. J., Ross R. A., Kwan M., Triche T. J., Miser J. S., Israel M. A. Indistinguishable patterns of protooncogene expression in two distinct but closely related tumors: Ewing's sarcoma and neuroepithelioma. Cancer Res. 1988 Aug 1;48(15):4307–4311. [PubMed] [Google Scholar]
  16. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mitchell E. L., White G. R., Santibanez-Koref M. F., Varley J. M., Heighway J. Mapping of gene loci in the Q13-Q15 region of chromosome 12. Chromosome Res. 1995 Jun;3(4):261–262. doi: 10.1007/BF00713052. [DOI] [PubMed] [Google Scholar]
  18. Mugneret F., Lizard S., Aurias A., Turc-Carel C. Chromosomes in Ewing's sarcoma. II. Nonrandom additional changes, trisomy 8 and der(16)t(1;16). Cancer Genet Cytogenet. 1988 Jun;32(2):239–245. doi: 10.1016/0165-4608(88)90286-5. [DOI] [PubMed] [Google Scholar]
  19. Navarro S., Cavazzana A. O., Llombart-Bosch A., Triche T. J. Comparison of Ewing's sarcoma of bone and peripheral neuroepithelioma. An immunocytochemical and ultrastructural analysis of two primitive neuroectodermal neoplasms. Arch Pathol Lab Med. 1994 Jun;118(6):608–615. [PubMed] [Google Scholar]
  20. Presland R. B., Haydock P. V., Fleckman P., Nirunsuksiri W., Dale B. A. Characterization of the human epidermal profilaggrin gene. Genomic organization and identification of an S-100-like calcium binding domain at the amino terminus. J Biol Chem. 1992 Nov 25;267(33):23772–23781. [PubMed] [Google Scholar]
  21. Smith S. H., Weiss S. W., Jankowski S. A., Coccia M. A., Meltzer P. S. SAS amplification in soft tissue sarcomas. Cancer Res. 1992 Jul 1;52(13):3746–3749. [PubMed] [Google Scholar]
  22. Suijkerbuijk R. F., Olde Weghuis D. E., Van den Berg M., Pedeutour F., Forus A., Myklebost O., Glier C., Turc-Carel C., Geurts van Kessel A. Comparative genomic hybridization as a tool to define two distinct chromosome 12-derived amplification units in well-differentiated liposarcomas. Genes Chromosomes Cancer. 1994 Apr;9(4):292–295. doi: 10.1002/gcc.2870090410. [DOI] [PubMed] [Google Scholar]
  23. Szymanska J., Mandahl N., Mertens F., Tarkkanen M., Karaharju E., Knuutila S. Ring chromosomes in parosteal osteosarcoma contain sequences from 12q13-15: a combined cytogenetic and comparative genomic hybridization study. Genes Chromosomes Cancer. 1996 May;16(1):31–34. doi: 10.1002/(SICI)1098-2264(199605)16:1<31::AID-GCC4>3.0.CO;2-4. [DOI] [PubMed] [Google Scholar]
  24. Szymanska J., Tarkkanen M., Wiklund T., Virolainen M., Blomqvist C., Asko-Seljavaara S., Tukiainen E., Elomaa I., Knuutila S. Gains and losses of DNA sequences in liposarcomas evaluated by comparative genomic hybridization. Genes Chromosomes Cancer. 1996 Feb;15(2):89–94. doi: 10.1002/(SICI)1098-2264(199602)15:2<89::AID-GCC2>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar]
  25. Tarkkanen M., Kaipainen A., Karaharju E., Böhling T., Szymanska J., Heliö H., Kivioja A., Elomaa I., Knuutila S. Cytogenetic study of 249 consecutive patients examined for a bone tumor. Cancer Genet Cytogenet. 1993 Jul 1;68(1):1–21. doi: 10.1016/0165-4608(93)90068-w. [DOI] [PubMed] [Google Scholar]
  26. Tarkkanen M., Karhu R., Kallioniemi A., Elomaa I., Kivioja A. H., Nevalainen J., Böhling T., Karaharju E., Hyytinen E., Knuutila S. Gains and losses of DNA sequences in osteosarcomas by comparative genomic hybridization. Cancer Res. 1995 Mar 15;55(6):1334–1338. [PubMed] [Google Scholar]
  27. Turc-Carel C., Aurias A., Mugneret F., Lizard S., Sidaner I., Volk C., Thiery J. P., Olschwang S., Philip I., Berger M. P. Chromosomes in Ewing's sarcoma. I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12). Cancer Genet Cytogenet. 1988 Jun;32(2):229–238. doi: 10.1016/0165-4608(88)90285-3. [DOI] [PubMed] [Google Scholar]
  28. Wolf M., Aaltonen L. A., Szymanska J., Tarkkanen M., Blomqvist C., Berner J. M., Myklebost O., Knuutila S. Complexity of 12q13-22 amplicon in liposarcoma: microsatellite repeat analysis. Genes Chromosomes Cancer. 1997 Jan;18(1):66–70. doi: 10.1002/(sici)1098-2264(199701)18:1<66::aid-gcc8>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  29. Zucman J., Melot T., Desmaze C., Ghysdael J., Plougastel B., Peter M., Zucker J. M., Triche T. J., Sheer D., Turc-Carel C. Combinatorial generation of variable fusion proteins in the Ewing family of tumours. EMBO J. 1993 Dec;12(12):4481–4487. doi: 10.1002/j.1460-2075.1993.tb06137.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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