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. 1994 Dec;145(6):1296–1300.

Reverse transcriptase polymerase chain reaction for the Ki-1 anaplastic large cell lymphoma-associated t(2;5) translocation in Hodgkin's disease.

M Ladanyi 1, G Cavalchire 1, S W Morris 1, J Downing 1, D A Filippa 1
PMCID: PMC1887484  PMID: 7527617

Abstract

Hodgkin's disease (HD) and Ki-1 positive anaplastic large cell lymphoma (Ki-1 ALCL) appear pathologically and immunohistochemically related, and a common histogenesis has been postulated in at least some cases. The breakpoints of the t(2;5) (p23;q35) [corrected] translocation, which is reported in about 40% of Ki-1 ALCL, have recently been cloned. They involve a novel tyrosine kinase gene, ALK, at 2p23 and the nucleophosmin gene, NPM, at 5q35. Reverse transcriptase polymerase chain reaction (RT-PCR) using NPM and ALK primers consistently detects a fusion product in Ki-1 ALCL cases with the translocation. To determine if this tumor-specific genetic alteration also occurs in HD, we performed NPM-ALK RT-PCR on RNA samples extracted from 40 lymph node biopsies of HD (25 nodular sclerosis, 11 mixed cellularity, 2 lymphocyte depleted, 2 lymphocyte predominant). Using control samples, the sensitivity of the NPM-ALK RT-PCR assay was shown to be at least 1:10(4). Amplifiable template was confirmed in all samples by RT-PCR using beta-actin primers. None of the 40 cases showed the expected 177-bp RT-PCR product indicative of the translocation. We conclude that the most common primary genetic alteration in Ki-1 ALCL, the t(2;5), is absent or very infrequent in typical cases of HD. These results further support the concept that HD and Ki-1 ALCL are pathogenetically distinct entities.

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Selected References

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

  1. Bullrich F., Morris S. W., Hummel M., Pileri S., Stein H., Croce C. M. Nucleophosmin (NPM) gene rearrangements in Ki-1-positive lymphomas. Cancer Res. 1994 Jun 1;54(11):2873–2877. [PubMed] [Google Scholar]
  2. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  3. Delabie J., Shipman R., Brüggen J., De Strooper B., van Leuven F., Tarcsay L., Cerletti N., Odink K., Diehl V., Bilbe G. Expression of the novel intermediate filament-associated protein restin in Hodgkin's disease and anaplastic large-cell lymphoma. Blood. 1992 Dec 1;80(11):2891–2896. [PubMed] [Google Scholar]
  4. Dürkop H., Latza U., Hummel M., Eitelbach F., Seed B., Stein H. Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease. Cell. 1992 Feb 7;68(3):421–427. doi: 10.1016/0092-8674(92)90180-k. [DOI] [PubMed] [Google Scholar]
  5. Ebrahim S. A., Ladanyi M., Desai S. B., Offit K., Jhanwar S. C., Filippa D. A., Lieberman P. H., Chaganti R. S. Immunohistochemical, molecular, and cytogenetic analysis of a consecutive series of 20 peripheral T-cell lymphomas and lymphomas of uncertain lineage, including 12 Ki-1 positive lymphomas. Genes Chromosomes Cancer. 1990 May;2(1):27–35. doi: 10.1002/gcc.2870020106. [DOI] [PubMed] [Google Scholar]
  6. Frizzera G. The distinction of Hodgkin's disease from anaplastic large cell lymphoma. Semin Diagn Pathol. 1992 Nov;9(4):291–296. [PubMed] [Google Scholar]
  7. Greer J. P., Kinney M. C., Collins R. D., Salhany K. E., Wolff S. N., Hainsworth J. D., Flexner J. M., Stein R. S. Clinical features of 31 patients with Ki-1 anaplastic large-cell lymphoma. J Clin Oncol. 1991 Apr;9(4):539–547. doi: 10.1200/JCO.1991.9.4.539. [DOI] [PubMed] [Google Scholar]
  8. Gruss H. J., Boiani N., Williams D. E., Armitage R. J., Smith C. A., Goodwin R. G. Pleiotropic effects of the CD30 ligand on CD30-expressing cells and lymphoma cell lines. Blood. 1994 Apr 15;83(8):2045–2056. [PubMed] [Google Scholar]
  9. Herbst H., Tippelmann G., Anagnostopoulos I., Gerdes J., Schwarting R., Boehm T., Pileri S., Jones D. B., Stein H. Immunoglobulin and T-cell receptor gene rearrangements in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma: dissociation between phenotype and genotype. Leuk Res. 1989;13(2):103–116. doi: 10.1016/0145-2126(89)90134-3. [DOI] [PubMed] [Google Scholar]
  10. Ladanyi M., Parsa N. Z., Offit K., Wachtel M. S., Filippa D. A., Jhanwar S. C. Clonal cytogenetic abnormalities in Hodgkin's disease. Genes Chromosomes Cancer. 1991 Jul;3(4):294–299. doi: 10.1002/gcc.2870030408. [DOI] [PubMed] [Google Scholar]
  11. Leoncini L., Del Vecchio M. T., Kraft R., Megha T., Barbini P., Cevenini G., Poggi S., Pileri S., Tosi P., Cottier H. Hodgkin's disease and CD30-positive anaplastic large cell lymphomas--a continuous spectrum of malignant disorders. A quantitative morphometric and immunohistologic study. Am J Pathol. 1990 Nov;137(5):1047–1057. [PMC free article] [PubMed] [Google Scholar]
  12. Mason D. Y., Bastard C., Rimokh R., Dastugue N., Huret J. L., Kristoffersson U., Magaud J. P., Nezelof C., Tilly H., Vannier J. P. CD30-positive large cell lymphomas ('Ki-1 lymphoma') are associated with a chromosomal translocation involving 5q35. Br J Haematol. 1990 Feb;74(2):161–168. doi: 10.1111/j.1365-2141.1990.tb02560.x. [DOI] [PubMed] [Google Scholar]
  13. Merz H., Houssiau F. A., Orscheschek K., Renauld J. C., Fliedner A., Herin M., Noel H., Kadin M., Mueller-Hermelink H. K., Van Snick J. Interleukin-9 expression in human malignant lymphomas: unique association with Hodgkin's disease and large cell anaplastic lymphoma. Blood. 1991 Sep 1;78(5):1311–1317. [PubMed] [Google Scholar]
  14. Morris S. W., Kirstein M. N., Valentine M. B., Dittmer K. G., Shapiro D. N., Saltman D. L., Look A. T. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science. 1994 Mar 4;263(5151):1281–1284. doi: 10.1126/science.8122112. [DOI] [PubMed] [Google Scholar]
  15. Ng S. Y., Gunning P., Eddy R., Ponte P., Leavitt J., Shows T., Kedes L. Evolution of the functional human beta-actin gene and its multi-pseudogene family: conservation of noncoding regions and chromosomal dispersion of pseudogenes. Mol Cell Biol. 1985 Oct;5(10):2720–2732. doi: 10.1128/mcb.5.10.2720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. O'Connor N. T., Stein H., Gatter K. C., Wainscoat J. S., Crick J., Al Saati T., Falini B., Delsol G., Mason D. Y. Genotypic analysis of large cell lymphomas which express the Ki-1 antigen. Histopathology. 1987 Jul;11(7):733–740. doi: 10.1111/j.1365-2559.1987.tb02687.x. [DOI] [PubMed] [Google Scholar]
  17. Perkins P. L., Ross C. W., Schnitzer B. CD30-positive, anaplastic large-cell lymphomas that express CD15 but lack CD45. A possible diagnostic pitfall. Arch Pathol Lab Med. 1992 Nov;116(11):1192–1196. [PubMed] [Google Scholar]
  18. Pinto A., Gloghini A., Gattei V., Aldinucci D., Zagonel V., Carbone A. Expression of the c-kit receptor in human lymphomas is restricted to Hodgkin's disease and CD30+ anaplastic large cell lymphomas. Blood. 1994 Feb 1;83(3):785–792. [PubMed] [Google Scholar]
  19. Rimokh R., Magaud J. P., Berger F., Samarut J., Coiffier B., Germain D., Mason D. Y. A translocation involving a specific breakpoint (q35) on chromosome 5 is characteristic of anaplastic large cell lymphoma ('Ki-1 lymphoma'). Br J Haematol. 1989 Jan;71(1):31–36. doi: 10.1111/j.1365-2141.1989.tb06270.x. [DOI] [PubMed] [Google Scholar]
  20. Rosso R., Paulli M., Magrini U., Kindl S., Boveri E., Volpato G., Poggi S., Baglioni P., Pileri S. Anaplastic large cell lymphoma, CD30/Ki-1 positive, expressing the CD15/Leu-M1 antigen. Immunohistochemical and morphological relationships to Hodgkin's disease. Virchows Arch A Pathol Anat Histopathol. 1990;416(3):229–235. doi: 10.1007/BF01678982. [DOI] [PubMed] [Google Scholar]
  21. Stein H., Mason D. Y., Gerdes J., O'Connor N., Wainscoat J., Pallesen G., Gatter K., Falini B., Delsol G., Lemke H. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood. 1985 Oct;66(4):848–858. [PubMed] [Google Scholar]
  22. Thangavelu M., Le Beau M. M. Chromosomal abnormalities in Hodgkin's disease. Hematol Oncol Clin North Am. 1989 Jun;3(2):221–236. [PubMed] [Google Scholar]
  23. Tilly H., Bastard C., Delastre T., Duval C., Bizet M., Lenormand B., Daucé J. P., Monconduit M., Piguet H. Cytogenetic studies in untreated Hodgkin's disease. Blood. 1991 Mar 15;77(6):1298–1304. [PubMed] [Google Scholar]
  24. Tsurumi H., Takahashi T., Moriwaki H., Muto Y. CD30/Ki-1-positive anaplastic large cell lymphoma preceded by Hodgkin's disease. Int J Hematol. 1992 Aug;56(1):99–102. [PubMed] [Google Scholar]
  25. Weiss L. M., Chang K. L. Molecular biologic studies of Hodgkin's disease. Semin Diagn Pathol. 1992 Nov;9(4):272–278. [PubMed] [Google Scholar]

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