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Molecular Pathology : MP logoLink to Molecular Pathology : MP
. 1998 Oct;51(5):262–267. doi: 10.1136/mp.51.5.262

Analysis of the frequency of microsatellite instability and p53 gene mutation in splenic marginal zone and MALT lymphomas.

M Sol Mateo 1, M Mollejo 1, R Villuendas 1, P Algara 1, M Sánchez-Beato 1, B Martinez-Delgado 1, P Martínez 1, M A Piris 1
PMCID: PMC395649  PMID: 10193520

Abstract

AIMS: Studies of the genetic characteristics of splenic marginal zone lymphoma (SMZL) have failed to identify genetic changes specific to this tumour. Microsatellite instability is a type of genomic instability associated with different types of human cancer. Although microsatellite instability is rare in B cell non-Hodgkin's lymphomas, it has been found in some specific subsets, such as marginal zone lymphomas arising in mucosa associated lymphoid tissue (MALT), where an association with p53 mutation has been described. Because it has been proposed that SMZL and MALT are close in histogenetic terms, this study investigated the comparative frequency of microsatellite instability and p53 mutation in patients with SMZL and MALT lymphomas. METHODS: Microsatellite instability was investigated using seven microsatellite marker loci in 14 patients with SMZL and 20 patients with MALT lymphomas. In an attempt to clarify the role of p53 gene mutation in the pathogenesis of SMZL, exons 5-8 were also investigated by polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) and direct sequencing in a total of 20 patients with SMZL and 22 patients with MALT lymphomas. RESULTS: Microsatellite instability was not detected in patients with SMZL, although five of 20 patients with MALT lymphomas had microsatellite instability. The frequency of p53 mutation was low in both series (two of 20 patients with SMZL and one of 22 patients with MALT lymphomas). No significant association was found between p53 mutation and microsatellite instability. CONCLUSIONS: These results indicate that microsatellite instability is not associated with the molecular pathogenesis of SMZL, confirming the relatively increased frequency of microsatellite instability in MALT lymphomas, and perhaps suggesting that MALT and SMZL have different mechanisms of tumorigenesis.

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Selected References

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  1. Aaltonen L. A., Peltomäki P., Leach F. S., Sistonen P., Pylkkänen L., Mecklin J. P., Järvinen H., Powell S. M., Jen J., Hamilton S. R. Clues to the pathogenesis of familial colorectal cancer. Science. 1993 May 7;260(5109):812–816. doi: 10.1126/science.8484121. [DOI] [PubMed] [Google Scholar]
  2. Baldini L., Fracchiolla N. S., Cro L. M., Trecca D., Romitti L., Polli E., Maiolo A. T., Neri A. Frequent p53 gene involvement in splenic B-cell leukemia/lymphomas of possible marginal zone origin. Blood. 1994 Jul 1;84(1):270–278. [PubMed] [Google Scholar]
  3. Bedi G. C., Westra W. H., Farzadegan H., Pitha P. M., Sidransky D. Microsatellite instability in primary neoplasms from HIV + patients. Nat Med. 1995 Jan;1(1):65–68. doi: 10.1038/nm0195-65. [DOI] [PubMed] [Google Scholar]
  4. Brentnall T. A., Crispin D. A., Bronner M. P., Cherian S. P., Hueffed M., Rabinovitch P. S., Rubin C. E., Haggitt R. C., Boland C. R. Microsatellite instability in nonneoplastic mucosa from patients with chronic ulcerative colitis. Cancer Res. 1996 Mar 15;56(6):1237–1240. [PubMed] [Google Scholar]
  5. Bronner C. E., Baker S. M., Morrison P. T., Warren G., Smith L. G., Lescoe M. K., Kane M., Earabino C., Lipford J., Lindblom A. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature. 1994 Mar 17;368(6468):258–261. doi: 10.1038/368258a0. [DOI] [PubMed] [Google Scholar]
  6. Brynes R. K., Almaguer P. D., Leathery K. E., McCourty A., Arber D. A., Medeiros L. J., Nathwani B. N. Numerical cytogenetic abnormalities of chromosomes 3, 7, and 12 in marginal zone B-cell lymphomas. Mod Pathol. 1996 Oct;9(10):995–1000. [PubMed] [Google Scholar]
  7. Cottu P. H., Muzeau F., Estreicher A., Fléjou J. F., Iggo R., Thomas G., Hamelin R. Inverse correlation between RER+ status and p53 mutation in colorectal cancer cell lines. Oncogene. 1996 Dec 19;13(12):2727–2730. [PubMed] [Google Scholar]
  8. De Vita S., Gasparotto D., Pivetta B., Vukosavljevic T., Zagonel V., Carbone A., Boiocchi M. Rarity of microsatellite genomic instability in B-cell non-Hodgkin's lymphomas in hepatitis C virus-infected patients. Br J Haematol. 1997 May;97(2):463–465. doi: 10.1046/j.1365-2141.1997.252670.x. [DOI] [PubMed] [Google Scholar]
  9. Dierlamm J., Michaux L., Wlodarska I., Pittaluga S., Zeller W., Stul M., Criel A., Thomas J., Boogaerts M., Delaere P. Trisomy 3 in marginal zone B-cell lymphoma: a study based on cytogenetic analysis and fluorescence in situ hybridization. Br J Haematol. 1996 Apr;93(1):242–249. doi: 10.1046/j.1365-2141.1996.522522.x. [DOI] [PubMed] [Google Scholar]
  10. Dierlamm J., Pittaluga S., Wlodarska I., Stul M., Thomas J., Boogaerts M., Michaux L., Driessen A., Mecucci C., Cassiman J. J. Marginal zone B-cell lymphomas of different sites share similar cytogenetic and morphologic features. Blood. 1996 Jan 1;87(1):299–307. [PubMed] [Google Scholar]
  11. Du M., Peng H., Singh N., Isaacson P. G., Pan L. The accumulation of p53 abnormalities is associated with progression of mucosa-associated lymphoid tissue lymphoma. Blood. 1995 Dec 15;86(12):4587–4593. [PubMed] [Google Scholar]
  12. Fey M. F., Pilkington S. P., Summers C., Wainscoat J. S. Molecular diagnosis of haematological disorders using DNA from stored bone marrow slides. Br J Haematol. 1987 Dec;67(4):489–492. doi: 10.1111/j.1365-2141.1987.tb06174.x. [DOI] [PubMed] [Google Scholar]
  13. Fishel R., Lescoe M. K., Rao M. R., Copeland N. G., Jenkins N. A., Garber J., Kane M., Kolodner R. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993 Dec 3;75(5):1027–1038. doi: 10.1016/0092-8674(93)90546-3. [DOI] [PubMed] [Google Scholar]
  14. Gaidano G., Ballerini P., Gong J. Z., Inghirami G., Neri A., Newcomb E. W., Magrath I. T., Knowles D. M., Dalla-Favera R. p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5413–5417. doi: 10.1073/pnas.88.12.5413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gaidano G., Pastore C., Gloghini A., Capello D., Tirelli U., Saglio G., Carbone A. Microsatellite instability in KSHV/HHV-8 positive body-cavity-based lymphoma. Hum Pathol. 1997 Jun;28(6):748–750. doi: 10.1016/s0046-8177(97)90187-8. [DOI] [PubMed] [Google Scholar]
  16. Gamberi B., Gaidano G., Parsa N., Carbone A., Roncella S., Knowles D. M., Louie D. C., Shibata D., Chaganti R. S., Dalla-Favera R. Microsatellite instability is rare in B-cell non-Hodgkin's lymphomas. Blood. 1997 Feb 1;89(3):975–979. [PubMed] [Google Scholar]
  17. Gartenhaus R., Johns M. M., 3rd, Wang P., Rai K., Sidransky D. Mutator phenotype in a subset of chronic lymphocytic leukemia. Blood. 1996 Jan 1;87(1):38–41. [PubMed] [Google Scholar]
  18. Hammer R. D., Glick A. D., Greer J. P., Collins R. D., Cousar J. B. Splenic marginal zone lymphoma. A distinct B-cell neoplasm. Am J Surg Pathol. 1996 May;20(5):613–626. doi: 10.1097/00000478-199605000-00008. [DOI] [PubMed] [Google Scholar]
  19. Harris N. L., Jaffe E. S., Stein H., Banks P. M., Chan J. K., Cleary M. L., Delsol G., De Wolf-Peeters C., Falini B., Gatter K. C. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994 Sep 1;84(5):1361–1392. [PubMed] [Google Scholar]
  20. Hollema H., Visser L., Poppema S. Small lymphocytic lymphomas with predominant splenomegaly: a comparison of immunophenotypes with cases of predominant lymphadenopathy. Mod Pathol. 1991 Nov;4(6):712–717. [PubMed] [Google Scholar]
  21. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  22. Ionov Y., Peinado M. A., Malkhosyan S., Shibata D., Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993 Jun 10;363(6429):558–561. doi: 10.1038/363558a0. [DOI] [PubMed] [Google Scholar]
  23. Isaacson P. G., Matutes E., Burke M., Catovsky D. The histopathology of splenic lymphoma with villous lymphocytes. Blood. 1994 Dec 1;84(11):3828–3834. [PubMed] [Google Scholar]
  24. Kisseljov F., Semionova L., Samoylova E., Mazurenko N., Komissarova E., Zourbitskaya V., Gritzko T., Kozachenko V., Netchushkin M., Petrov S. Instability of chromosome 6 microsatellite repeats in human cervical tumors carrying papillomavirus sequences. Int J Cancer. 1996 Dec 20;69(6):484–487. doi: 10.1002/(SICI)1097-0215(19961220)69:6<484::AID-IJC12>3.0.CO;2-1. [DOI] [PubMed] [Google Scholar]
  25. Larson R. S., Scott M. A., McCurley T. L., Vnencak-Jones C. L. Microsatellite analysis of posttransplant lymphoproliferative disorders: determination of donor/recipient origin and identification of putative lymphomagenic mechanism. Cancer Res. 1996 Oct 1;56(19):4378–4381. [PubMed] [Google Scholar]
  26. Leach F. S., Nicolaides N. C., Papadopoulos N., Liu B., Jen J., Parsons R., Peltomäki P., Sistonen P., Aaltonen L. A., Nyström-Lahti M. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993 Dec 17;75(6):1215–1225. doi: 10.1016/0092-8674(93)90330-s. [DOI] [PubMed] [Google Scholar]
  27. Levy V., Miller C., Koeffler H. P., Said J. W. p53 in lymphomas of mucosal-associated lymphoid tissues. Mod Pathol. 1996 Mar;9(3):245–248. [PubMed] [Google Scholar]
  28. Lothe R. A., Peltomäki P., Meling G. I., Aaltonen L. A., Nyström-Lahti M., Pylkkänen L., Heimdal K., Andersen T. I., Møller P., Rognum T. O. Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Res. 1993 Dec 15;53(24):5849–5852. [PubMed] [Google Scholar]
  29. Mao L., Lee D. J., Tockman M. S., Erozan Y. S., Askin F., Sidransky D. Microsatellite alterations as clonal markers for the detection of human cancer. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9871–9875. doi: 10.1073/pnas.91.21.9871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mao L., Schoenberg M. P., Scicchitano M., Erozan Y. S., Merlo A., Schwab D., Sidransky D. Molecular detection of primary bladder cancer by microsatellite analysis. Science. 1996 Feb 2;271(5249):659–662. doi: 10.1126/science.271.5249.659. [DOI] [PubMed] [Google Scholar]
  31. Mollejo M., Lloret E., Menárguez J., Piris M. A., Isaacson P. G. Lymph node involvement by splenic marginal zone lymphoma: morphological and immunohistochemical features. Am J Surg Pathol. 1997 Jul;21(7):772–780. doi: 10.1097/00000478-199707000-00005. [DOI] [PubMed] [Google Scholar]
  32. Mollejo M., Menárguez J., Lloret E., Sánchez A., Campo E., Algara P., Cristóbal E., Sánchez E., Piris M. A. Splenic marginal zone lymphoma: a distinctive type of low-grade B-cell lymphoma. A clinicopathological study of 13 cases. Am J Surg Pathol. 1995 Oct;19(10):1146–1157. [PubMed] [Google Scholar]
  33. Nicolaides N. C., Papadopoulos N., Liu B., Wei Y. F., Carter K. C., Ruben S. M., Rosen C. A., Haseltine W. A., Fleischmann R. D., Fraser C. M. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature. 1994 Sep 1;371(6492):75–80. doi: 10.1038/371075a0. [DOI] [PubMed] [Google Scholar]
  34. Nigro J. M., Baker S. J., Preisinger A. C., Jessup J. M., Hostetter R., Cleary K., Bigner S. H., Davidson N., Baylin S., Devilee P. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989 Dec 7;342(6250):705–708. doi: 10.1038/342705a0. [DOI] [PubMed] [Google Scholar]
  35. Pabst T., Schwaller J., Bellomo M. J., Oestreicher M., Mühlematter D., Tichelli A., Tobler A., Fey M. F. Frequent clonal loss of heterozygosity but scarcity of microsatellite instability at chromosomal breakpoint cluster regions in adult leukemias. Blood. 1996 Aug 1;88(3):1026–1034. [PubMed] [Google Scholar]
  36. Papadopoulos N., Nicolaides N. C., Wei Y. F., Ruben S. M., Carter K. C., Rosen C. A., Haseltine W. A., Fleischmann R. D., Fraser C. M., Adams M. D. Mutation of a mutL homolog in hereditary colon cancer. Science. 1994 Mar 18;263(5153):1625–1629. doi: 10.1126/science.8128251. [DOI] [PubMed] [Google Scholar]
  37. Peltomäki P., Lothe R. A., Aaltonen L. A., Pylkkänen L., Nyström-Lahti M., Seruca R., David L., Holm R., Ryberg D., Haugen A. Microsatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal carcinoma syndrome. Cancer Res. 1993 Dec 15;53(24):5853–5855. [PubMed] [Google Scholar]
  38. Peng H., Chen G., Du M., Singh N., Isaacson P. G., Pan L. Replication error phenotype and p53 gene mutation in lymphomas of mucosa-associated lymphoid tissue. Am J Pathol. 1996 Feb;148(2):643–648. [PMC free article] [PubMed] [Google Scholar]
  39. Randerson J., Cawkwell L., Jack A., Child J. A., Lewis F., Hall N., Johnson P., Evans P., Barrans S., Morgan G. J. Microsatellite instability in follicle centre cell lymphoma. Br J Haematol. 1996 Apr;93(1):160–162. doi: 10.1046/j.1365-2141.1996.456994.x. [DOI] [PubMed] [Google Scholar]
  40. Renault B., Calistri D., Buonsanti G., Nanni O., Amadori D., Ranzani G. N. Microsatellite instability and mutations of p53 and TGF-beta RII genes in gastric cancer. Hum Genet. 1996 Nov;98(5):601–607. doi: 10.1007/s004390050267. [DOI] [PubMed] [Google Scholar]
  41. Rhyu M. G., Park W. S., Meltzer S. J. Microsatellite instability occurs frequently in human gastric carcinoma. Oncogene. 1994 Jan;9(1):29–32. [PubMed] [Google Scholar]
  42. Robledo M., Martinez B., Arranz E., Trujillo M. J., Gonzalez Ageitos A., Rivas C., Benitez J. Genetic instability of microsatellites in hematological neoplasms. Leukemia. 1995 Jun;9(6):960–964. [PubMed] [Google Scholar]
  43. Salvucci M., Lemoine A., Azoulay D., Sebagh M., Bismuth H., Reyns M., May E., Debuire B. Frequent microsatellite instability in post hepatitis B viral cirrhosis. Oncogene. 1996 Dec 19;13(12):2681–2685. [PubMed] [Google Scholar]
  44. Schmid C., Kirkham N., Diss T., Isaacson P. G. Splenic marginal zone cell lymphoma. Am J Surg Pathol. 1992 May;16(5):455–466. doi: 10.1097/00000478-199205000-00004. [DOI] [PubMed] [Google Scholar]
  45. Solé F., Woessner S., Florensa L., Espinet B., Mollejo M., Martín P., Piris M. A. Frequent involvement of chromosomes 1, 3, 7 and 8 in splenic marginal zone B-cell lymphoma. Br J Haematol. 1997 Aug;98(2):446–449. doi: 10.1046/j.1365-2141.1997.2163033.x. [DOI] [PubMed] [Google Scholar]
  46. Thibodeau S. N., Bren G., Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993 May 7;260(5109):816–819. doi: 10.1126/science.8484122. [DOI] [PubMed] [Google Scholar]
  47. Villuendas R., Pezzella F., Gatter K., Algara P., Sánchez-Beato M., Martínez P., Martínez J. C., Muñoz K., García P., Sánchez L. p21WAF1/CIP1 and MDM2 expression in non-Hodgkin's lymphoma and their relationship to p53 status: a p53+, MDM2-, p21-immunophenotype associated with missense p53 mutations. J Pathol. 1997 Jan;181(1):51–61. doi: 10.1002/(SICI)1096-9896(199701)181:1<51::AID-PATH689>3.0.CO;2-N. [DOI] [PubMed] [Google Scholar]
  48. Villuendas R., Piris M. A., Algara P., Sánchez-Beato M., Sánchez-Verde L., Martinez J. C., Orradre J. L., García P., Lopez C., Martinez P. The expression of p53 protein in non-Hodgkin's lymphomas is not always dependent on p53 gene mutations. Blood. 1993 Nov 15;82(10):3151–3156. [PubMed] [Google Scholar]
  49. Villuendas R., Piris M. A., Orradre J. L., Mollejo M., Rodriguez R., Morente M. Different bcl-2 protein expression in high-grade B-cell lymphomas derived from lymph node or mucosa-associated lymphoid tissue. Am J Pathol. 1991 Nov;139(5):989–993. [PMC free article] [PubMed] [Google Scholar]
  50. Volpe G., Gamberi B., Pastore C., Roetto A., Pautasso M., Parvis G., Camaschella C., Mazza U., Saglio G., Gaidano G. Analysis of microsatellite instability in chronic lymphoproliferative disorders. Ann Hematol. 1996 Feb;72(2):67–71. doi: 10.1007/BF00641310. [DOI] [PubMed] [Google Scholar]
  51. Wada M., Bartram C. R., Nakamura H., Hachiya M., Chen D. L., Borenstein J., Miller C. W., Ludwig L., Hansen-Hagge T. E., Ludwig W. D. Analysis of p53 mutations in a large series of lymphoid hematologic malignancies of childhood. Blood. 1993 Nov 15;82(10):3163–3169. [PubMed] [Google Scholar]
  52. Weber J. L., Wong C. Mutation of human short tandem repeats. Hum Mol Genet. 1993 Aug;2(8):1123–1128. doi: 10.1093/hmg/2.8.1123. [DOI] [PubMed] [Google Scholar]
  53. Wooster R., Cleton-Jansen A. M., Collins N., Mangion J., Cornelis R. S., Cooper C. S., Gusterson B. A., Ponder B. A., von Deimling A., Wiestler O. D. Instability of short tandem repeats (microsatellites) in human cancers. Nat Genet. 1994 Feb;6(2):152–156. doi: 10.1038/ng0294-152. [DOI] [PubMed] [Google Scholar]
  54. Wotherspoon A. C., Finn T. M., Isaacson P. G. Trisomy 3 in low-grade B-cell lymphomas of mucosa-associated lymphoid tissue. Blood. 1995 Apr 15;85(8):2000–2004. [PubMed] [Google Scholar]

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