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. 2001 Feb;84(3):381–387. doi: 10.1054/bjoc.2000.1593

Loss of heterozygosity in the Hodgkin-Reed Sternberg cell line L1236

A Staratschek-Jox 1, R Kurt Thomas 1, T Zander 1, N Massoudi 1, M Kornacker 1, J Bullerdiek 2, C Fonatsch 3, V Diehl 1, J Wolf 1
PMCID: PMC2363750  PMID: 11161403

Abstract

Hodgkin-Reed Sternberg cells are derived from germinal centre B-cells in most cases. Somatic mutations affecting their rearranged immunoglobulin genes were detected, rendering potential functional rearrangements non-functional. Under physiological conditions such cells would be designated to undergo apoptosis within the germinal centre. In search for the specific transforming event that prevents Hodgkin-Reed Sternberg cells from programmed cell death, cytogenetic analyses were broadly performed but did not reveal specific chromosomal aberrations. Analysis of these cells on the molecular level is difficult to perform due to the scarcity of the cells in the lymphoma tissue and the given limitations of in situ studies. To overcome these limitations, the cell line L1236, known to be derived from Hodgkin-Reed Sternberg cells in situ, was chosen for allelotype analysis. Using a panel of microsatellite loci assigned to nearly all chromosomal arms, regions of loss of heterozygosity were detected on chromosomal arms 6p, 9q and 17p. The size of lost segments was estimated by amplification of additional microsatellite loci mapped to the respective regions. Further analyses of single Hodgkin-Reed Sternberg cells will reveal whether LOH affecting these regions is a recurrent event in HD and to which extent the smallest commonly affected region can be estimated. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: Hodgkin's disease, loss of heterozygosity, tumour suppressor gene

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Selected References

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  1. Bargou R. C., Emmerich F., Krappmann D., Bommert K., Mapara M. Y., Arnold W., Royer H. D., Grinstein E., Greiner A., Scheidereit C. Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin's disease tumor cells. J Clin Invest. 1997 Dec 15;100(12):2961–2969. doi: 10.1172/JCI119849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chattopadhyay P., Rathore A., Mathur M., Sarkar C., Mahapatra A. K., Sinha S. Loss of heterozygosity of a locus on 17p13.3, independent of p53, is associated with higher grades of astrocytic tumours. Oncogene. 1997 Aug 14;15(7):871–874. doi: 10.1038/sj.onc.1201238. [DOI] [PubMed] [Google Scholar]
  3. Falzetti D., Crescenzi B., Matteuci C., Falini B., Martelli M. F., Van Den Berghe H., Mecucci C. Genomic instability and recurrent breakpoints are main cytogenetic findings in Hodgkin's disease. Haematologica. 1999 Apr;84(4):298–305. [PubMed] [Google Scholar]
  4. Grebe S. K., McIver B., Hay I. D., Wu P. S., Maciel L. M., Drabkin H. A., Goellner J. R., Grant C. S., Jenkins R. B., Eberhardt N. L. Frequent loss of heterozygosity on chromosomes 3p and 17p without VHL or p53 mutations suggests involvement of unidentified tumor suppressor genes in follicular thyroid carcinoma. J Clin Endocrinol Metab. 1997 Nov;82(11):3684–3691. doi: 10.1210/jcem.82.11.4352. [DOI] [PubMed] [Google Scholar]
  5. Hasse U., Tinguely M., Leibundgut E. O., Cajot J. F., Garvin A. M., Tobler A., Borisch B., Fey M. F. Clonal loss of heterozygosity in microdissected Hodgkin and Reed-Sternberg cells. J Natl Cancer Inst. 1999 Sep 15;91(18):1581–1583. doi: 10.1093/jnci/91.18.1581. [DOI] [PubMed] [Google Scholar]
  6. Honchel R., McDonnell S., Schaid D. J., Thibodeau S. N. Tumor necrosis factor-alpha allelic frequency and chromosome 6 allelic imbalance in patients with colorectal cancer. Cancer Res. 1996 Jan 1;56(1):145–149. [PubMed] [Google Scholar]
  7. Jiménez P., Cantón J., Collado A., Cabrera T., Serrano A., Real L. M., García A., Ruiz-Cabello F., Garrido F. Chromosome loss is the most frequent mechanism contributing to HLA haplotype loss in human tumors. Int J Cancer. 1999 Sep 24;83(1):91–97. doi: 10.1002/(sici)1097-0215(19990924)83:1<91::aid-ijc17>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  8. Jox A., Zander T., Kornacker M., Kanzler H., Küppers R., Diehl V., Wolf J. Detection of identical Hodgkin-Reed Sternberg cell specific immunoglobulin gene rearrangements in a patient with Hodgkin's disease of mixed cellularity subtype at primary diagnosis and in relapse two and a half years later. Ann Oncol. 1998 Mar;9(3):283–287. doi: 10.1023/a:1008249214328. [DOI] [PubMed] [Google Scholar]
  9. Jungnickel B., Staratschek-Jox A., Bräuninger A., Spieker T., Wolf J., Diehl V., Hansmann M. L., Rajewsky K., Küppers R. Clonal deleterious mutations in the IkappaBalpha gene in the malignant cells in Hodgkin's lymphoma. J Exp Med. 2000 Jan 17;191(2):395–402. doi: 10.1084/jem.191.2.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kanzler H., Hansmann M. L., Kapp U., Wolf J., Diehl V., Rajewsky K., Küppers R. Molecular single cell analysis demonstrates the derivation of a peripheral blood-derived cell line (L1236) from the Hodgkin/Reed-Sternberg cells of a Hodgkin's lymphoma patient. Blood. 1996 Apr 15;87(8):3429–3436. [PubMed] [Google Scholar]
  11. Keen A. J., Knowles M. A. Definition of two regions of deletion on chromosome 9 in carcinoma of the bladder. Oncogene. 1994 Jul;9(7):2083–2088. [PubMed] [Google Scholar]
  12. Konishi H., Takahashi T., Kozaki K., Yatabe Y., Mitsudomi T., Fujii Y., Sugiura T., Matsuda H., Takahashi T., Takahashi T. Detailed deletion mapping suggests the involvement of a tumor suppressor gene at 17p13.3, distal to p53, in the pathogenesis of lung cancers. Oncogene. 1998 Oct 22;17(16):2095–2100. doi: 10.1038/sj.onc.1202128. [DOI] [PubMed] [Google Scholar]
  13. Küppers R., Rajewsky K. The origin of Hodgkin and Reed/Sternberg cells in Hodgkin's disease. Annu Rev Immunol. 1998;16:471–493. doi: 10.1146/annurev.immunol.16.1.471. [DOI] [PubMed] [Google Scholar]
  14. Lenoir G. M., Vuillaume M., Bonnardel C. The use of lymphomatous and lymphoblastoid cell lines in the study of Burkitt's lymphoma. IARC Sci Publ. 1985;(60):309–318. [PubMed] [Google Scholar]
  15. Liscia D. S., Morizio R., Venesio T., Palenzona C., Donadio M., Callahan R. Prognostic significance of loss of heterozygosity at loci on chromosome 17p13.3-ter in sporadic breast cancer is evidence for a putative tumour suppressor gene. Br J Cancer. 1999 May;80(5-6):821–826. doi: 10.1038/sj.bjc.6690427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Montesinos-Rongen M., Roers A., Küppers R., Rajewsky K., Hansmann M. L. Mutation of the p53 gene is not a typical feature of Hodgkin and Reed-Sternberg cells in Hodgkin's disease. Blood. 1999 Sep 1;94(5):1755–1760. [PubMed] [Google Scholar]
  17. Nagai H., Kinoshita T., Suzuki H., Hatano S., Murate T., Saito H. Identification and mapping of novel tumor suppressor loci on 6p in diffuse large B-cell non-Hodgkin's lymphoma. Genes Chromosomes Cancer. 1999 Jul;25(3):277–283. [PubMed] [Google Scholar]
  18. Osborne R. J., Leech V. Polymerase chain reaction allelotyping of human ovarian cancer. Br J Cancer. 1994 Mar;69(3):429–438. doi: 10.1038/bjc.1994.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Steichen-Gersdorf E., Baumgartner M., Kreczy A., Maier H., Fink F. M. Deletion mapping on chromosome 17p in medulloblastoma. Br J Cancer. 1997;76(10):1284–1287. doi: 10.1038/bjc.1997.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Weber-Matthiesen K., Deerberg J., Poetsch M., Grote W., Schlegelberger B. Numerical chromosome aberrations are present within the CD30+ Hodgkin and Reed-Sternberg cells in 100% of analyzed cases of Hodgkin's disease. Blood. 1995 Aug 15;86(4):1464–1468. [PubMed] [Google Scholar]
  21. Wolf J., Kapp U., Bohlen H., Kornacker M., Schoch C., Stahl B., Mücke S., von Kalle C., Fonatsch C., Schaefer H. E. Peripheral blood mononuclear cells of a patient with advanced Hodgkin's lymphoma give rise to permanently growing Hodgkin-Reed Sternberg cells. Blood. 1996 Apr 15;87(8):3418–3428. [PubMed] [Google Scholar]

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