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. 1993 Jan;67(1):128–133. doi: 10.1038/bjc.1993.22

Diagnosis of Ewing's sarcoma and peripheral neuroectodermal tumour based on the detection of t(11;22) using fluorescence in situ hybridisation.

C Taylor 1, K Patel 1, T Jones 1, F Kiely 1, B L De Stavola 1, D Sheer 1
PMCID: PMC1968231  PMID: 8381297

Abstract

Fluorescence in situ hybridisation (FISH) has been used increasingly for gene mapping and ordering probes on interphase and metaphase preparations. The association of consistent chromosomal aberrations with certain malignancies allows the possibility of using interphase cytogenetics as a diagnostic tool. In small round cell tumours of children accurate diagnosis may be difficult using existing methods. We have therefore evaluated the diagnostic potential of this technique when applied to the characteristic t(11;22) found in Ewing's sarcoma and peripheral neuroectodermal tumour (ES and PNET). Interphase nuclei were prepared from normal human foreskin fibroblasts (HFF), two Ewing's sarcoma cell lines and several fresh tumour biopsies. DNA probes each side of the breakpoint at 22q12 were labelled with biotin and digoxygenin, hybridised to chromosomes in interphase and detected in different colours. Measurements between pairs of signals arising from each copy of chromosome 22 were taken and statistical analysis performed. There was a highly significant difference (P < 0.0001) between the two populations of measurements obtained (from nuclei with and without the t(11;22)). Studying four tumours and one further ES line (blind) it was found that median values from 30 nuclei could correctly identify which samples contained the t(11;22). This application of interphase cytogenetics contributes a reliable, accurate and conceptually simple diagnostic test for ES and PNET. It may now be applied to other tumours with characteristic translocations, amplifications or deletions when suitable probes are available. This approach is likely to become a routine in clinical diagnosis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Budarf M., Emanuel B. S., Mohandas T., Goeddel D. V., Lowe D. G. Human differentiation-stimulating factor (leukemia inhibitory factor, human interleukin DA) gene maps distal to the Ewing sarcoma breakpoint on 22q. Cytogenet Cell Genet. 1989;52(1-2):19–22. doi: 10.1159/000132831. [DOI] [PubMed] [Google Scholar]
  2. Christiansen H., Lampert F. Tumour karyotype discriminates between good and bad prognostic outcome in neuroblastoma. Br J Cancer. 1988 Jan;57(1):121–126. doi: 10.1038/bjc.1988.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dewald G. W., Noel P., Dahl R. J., Spurbeck J. L. Chromosome abnormalities in malignant hematologic disorders. Mayo Clin Proc. 1985 Oct;60(10):675–689. doi: 10.1016/s0025-6196(12)60744-7. [DOI] [PubMed] [Google Scholar]
  4. Donner L. R. Cytogenetics and molecular biology of small round-cell tumors and related neoplasms. Current status. Cancer Genet Cytogenet. 1991 Jul 1;54(1):1–10. doi: 10.1016/0165-4608(91)90023-n. [DOI] [PubMed] [Google Scholar]
  5. Fletcher J. A., Kozakewich H. P., Hoffer F. A., Lage J. M., Weidner N., Tepper R., Pinkus G. S., Morton C. C., Corson J. M. Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumors. N Engl J Med. 1991 Feb 14;324(7):436–442. doi: 10.1056/NEJM199102143240702. [DOI] [PubMed] [Google Scholar]
  6. Gorman P. A., Malone M., Pritchard J., Sheer D. Cytogenetic analysis of primitive neuroectodermal tumors. Absence of the t(11;22) in two of three cases and a review of the literature. Cancer Genet Cytogenet. 1991 Jan;51(1):13–22. doi: 10.1016/0165-4608(91)90003-d. [DOI] [PubMed] [Google Scholar]
  7. Gough N. M., Gearing D. P., King J. A., Willson T. A., Hilton D. J., Nicola N. A., Metcalf D. Molecular cloning and expression of the human homologue of the murine gene encoding myeloid leukemia-inhibitory factor. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2623–2627. doi: 10.1073/pnas.85.8.2623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Landegent J. E., Jansen in de Wal N., Dirks R. W., Baao F., van der Ploeg M. Use of whole cosmid cloned genomic sequences for chromosomal localization by non-radioactive in situ hybridization. Hum Genet. 1987 Dec;77(4):366–370. doi: 10.1007/BF00291428. [DOI] [PubMed] [Google Scholar]
  9. Lawrence J. B., Singer R. H., McNeil J. A. Interphase and metaphase resolution of different distances within the human dystrophin gene. Science. 1990 Aug 24;249(4971):928–932. doi: 10.1126/science.2203143. [DOI] [PubMed] [Google Scholar]
  10. Pinkel D., Straume T., Gray J. W. Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. Proc Natl Acad Sci U S A. 1986 May;83(9):2934–2938. doi: 10.1073/pnas.83.9.2934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Selleri L., Hermanson G. G., Eubanks J. H., Lewis K. A., Evans G. A. Molecular localization of the t(11;22)(q24;q12) translocation of Ewing sarcoma by chromosomal in situ suppression hybridization. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):887–891. doi: 10.1073/pnas.88.3.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Shtalrid M., Talpaz M., Blick M., Romero P., Kantarjian H., Taylor K., Trujillo J., Schachner J., Gutterman J. U., Kurzrock R. Philadelphia-negative chronic myelogenous leukemia with breakpoint cluster region rearrangement: molecular analysis, clinical characteristics, and response to therapy. J Clin Oncol. 1988 Oct;6(10):1569–1575. doi: 10.1200/JCO.1988.6.10.1569. [DOI] [PubMed] [Google Scholar]
  13. Tkachuk D. C., Pinkel D., Kuo W. L., Weier H. U., Gray J. W. Clinical applications of fluorescence in situ hybridization. Genet Anal Tech Appl. 1991 Apr;8(2):67–74. doi: 10.1016/1050-3862(91)90051-r. [DOI] [PubMed] [Google Scholar]
  14. Tkachuk D. C., Westbrook C. A., Andreeff M., Donlon T. A., Cleary M. L., Suryanarayan K., Homge M., Redner A., Gray J., Pinkel D. Detection of bcr-abl fusion in chronic myelogeneous leukemia by in situ hybridization. Science. 1990 Oct 26;250(4980):559–562. doi: 10.1126/science.2237408. [DOI] [PubMed] [Google Scholar]
  15. Trask B., Pinkel D., van den Engh G. The proximity of DNA sequences in interphase cell nuclei is correlated to genomic distance and permits ordering of cosmids spanning 250 kilobase pairs. Genomics. 1989 Nov;5(4):710–717. doi: 10.1016/0888-7543(89)90112-2. [DOI] [PubMed] [Google Scholar]
  16. Weith A., Martinsson T., Cziepluch C., Brüderlein S., Amler L. C., Berthold F., Schwab M. Neuroblastoma consensus deletion maps to 1p36.1-2. Genes Chromosomes Cancer. 1989 Nov;1(2):159–166. doi: 10.1002/gcc.2870010209. [DOI] [PubMed] [Google Scholar]
  17. Whang-Peng J., Triche T. J., Knutsen T., Miser J., Douglass E. C., Israel M. A. Chromosome translocation in peripheral neuroepithelioma. N Engl J Med. 1984 Aug 30;311(9):584–585. doi: 10.1056/NEJM198408303110907. [DOI] [PubMed] [Google Scholar]
  18. Williams S. V., Jones T. A., Cottrell S., Zehetner G., Varesco L., Ward T., Thomas H., Lawson P. A., Solomon E., Bodmer W. F. Fine mapping of probes in the adenomatous polyposis coli region of chromosome 5 by in situ hybridization. Genes Chromosomes Cancer. 1991 Sep;3(5):382–389. doi: 10.1002/gcc.2870030509. [DOI] [PubMed] [Google Scholar]

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