MATERIAIS E MÉTODOS Pacientes e as amostras
6 Linfoma Multicêntrico Positivo Positivo 7
7 Linfoma Mediastinal NT4 NT 10 0
Controle Sem alterações Negativo Negativo 10 0
1LMA-M6a: leucemia eritroide aguda. 2 FeLV: vírus da leucemia felina. 3FIV: vírus da imunodeficiência
1MN: micronúcleo. 2NPBs: pontes nucleoplasmáticas. 3NBUDs: brotos nucleares. 4LMA-M6a: leucemia
eritroide aguda.
Quadro 2. Descrição das características morfológicas nucleares, ploidia e estado mitótico e de sobrevida de células de felinos com leucemia mieloide aguda M6a, linfoma multicêntrico e de um animal controle.
Células Animal
Controle LMA-M6a4 Linfoma
Mononuclear 989 889 932 Binuclear 7 8 16 Multinuclear 0 8 19 Mononuclear MN1 0 5 7 Binuclear MN 0 0 2 NPBs2 0 0 0 NBUDs3 0 3 7 Necrótica 1 12 8 Apoptótica 1 24 5 Mitótica 2 51 4 Total 1000 1000 1000
3CONCLUSÃO
A análise citogenética de células neoplásicas é importante para identificar alterações e estabelecer possíveis causas associadas ao desenvolvimento das neoplasias.
A monossomia do cromossomo E3 é uma alteração citogenética recorrente em felinos e envolve genes importantes no controle de ciclo celular, apoptose, reparo de DNA e supressão tumoral e sobrevida, processos associados à malignidade. A presença de micronúcleos está relacionada com a malignidade dos neoplasmas.
A citogenética convencional é adequada para identificar anomalias cromossômicas relacionadas com a etiopatogenia das neoplasias.
4REFERÊNCIAS
BISHOP, J. M. The molecular genetics of cancer. Science 235, 305. 1987.
BOAS, D. S. V.; Cariótipo multicolorido: mapeamento cromossômico através do uso de sondas de DNA fluorescentes. Revista Ceciliana, v. 1, n. 1, p. 1-17, Santa Cecília, 2009. BOUVARD, V., BAAN, R., STRAIF, K., GROSSE, Y., SECRETAN, B., EL GHISSASSI, F., BENBRAHIM TALLAA, L., GUHA, N., FREEMAN, C., GALICHET, L., et al. A review of human carcinogens-Part B: biological agents. Lancet Oncology 10, 321–322. 2009.
COSTA, U.M., REISCHAK, D., SCHMITT, A.C., RENCK, L., OLIVEIRA, E.S., FERREIRO, L. Detection of feline leukemiavirus (FeLV) antigen from 1992 to june 2000 by indirect immunofluorescence test in Porto Alegre, Rio Grande do Sul, Brasil. Virus Reviews. Research. 5, 94.
COUTO, C. G. Linfoma em cães e gatos., IN: NELSON, R. W.; COUTO, C. G. Medicina
interna de pequenos animais. 3ª Edição. Rio de Janeiro: Elsevier, 2006.
COUTO, C.G. Lymphoma in the cat and dog. In: NELSON, R.N. & COUTO, C.G. (Eds). Small animal internal medicine. 2009. (4th ed.). (pp. 1175-1186). Missouri: Mosby Elsevier. DALLA-FAVERA, R., BREGNI, M. & ERIKSON, J. Human c- myc one gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proceedings of the National Academy of Sciences. USA. 79, 7824. 1982.
DEVITT, J.J., MARANON, D.G., EHRHART, E.J., BACHAND, A.M., LANA, S.E. & LARUE, S.M. Correlations between numerical chromosomal aberrations in the tumor and peripheral blood in canine lymphoma. Cytogenetical and Genome Research, v. 124, p. 12– 18. 2009.
ERICHSEN, J.V., HECHT, W., LÖHBERG-GRUENE, C. & REINACHER, M. Cell lines derived from feline fibrossarcoma display unstable chromosomal aneuploidy and additionally centrosome number aberrations. Veterinary Pathology 49(9), 648-657. 2012.
FEARON, E. F. & VOGELSTEIN, B. A genetic model for colorectal tumorigenesis. Cell 61, 759. 1990.
FENECH, M. & MORLEY, A.A. Cytokinesis-block micronucleus method in human lymphocytes: effect of in vivo ageing and low-dose x-irradiation. Mutation Research. 161, 193–198. 1986.
FENECH, M. Cytokinesis-block micronucleus assay evolves into a ‘‘cytome’’ assay of chromosomal instability, mitotic dysfunction and cell death. Mutation Research. 600, 58–66. 2006.
FENECH, M. The advantages and disadvantages of the cytokinesis-block micronucleus method. Mutation Research. 392, 11–18. 1997.
FIGHERA R.A. & GRAÇA D.L. Sistema hematopoiético. In: SANTOS R.L. & ALESSI A.C. (Eds), Patologia Veterinária Brasileira. São Paulo: Roca, 2011. p.337-422
FORREST, D., ONIONS, D., LEES, G., NEIL, J.C. Altered structure and expression of c- myc
in feline T-cell tumours. Virology 158, 194–205. 1987.
FUJINO, Y., OHNO, K., TSUJIMOTO, H. Molecular pathogenesis of feline leukemia virus-induced malignancies: insertional mutagenesis. Veterinary Immunology Immunopathology 123, 138–143. 2008.
FUJINO, Y., LIAO, C.P., ZHAO, Y.S., PAN, J., MATHES, L.E., HAYES, K.A., OHNO, K., TSUJIMOTO, H., ROY-BURMAN, P. Identification of a novel common proviral integration site, flit-1, in feline leukemia virus induced thymic lymphoma. Virology 386, 16–22. 2009. GIEGER T. Alimentary Lymphoma in Cats and Dogs, Veterinary Clinical Small Animal 41, 419–432. 2011.
GOH, K.O., SMITH, R. A. & PROPER, J. S. Chromosomal aberrations in leukemic cats. Cornell Vet. 71, 43. 1981.
GRINDEM, C. B. & BUOEN, L. C. Cytogenetic analysis in nine leukaemic cats. Journal Comparative Pathology 101, 21. 1989.
GULINO, S. E. Chromosome abnormalities and oncogenesis in cat leukemias. Cancer Genetic Cytogenetic. 64, 149. 1992.
HALUSKA, F.G., TSUJIMOTO, Y., CROCE, C.M. The t(8:14) chromosome translocation of the Brukitt lymphoma cell line Daudi occurred during immunoglobulin gene rearrangement and involved the heavy chain diversity region. Proceedings of the National Academy of Sciences. USA. oct; 84(19): 6835-6839. 1987.
HANEY, S.M., BEAVER, L., TURREL, J., CLIFFORD, C.A., KLEIN, M.K., CRAWFORD, S., POULSON, J.M. & AZUMA, C. Survival analysis of 97 cats with nasal lymphoma: a multiinstitutional retrospective study (1986-2006). Journal of Veterinary Internal Medicine. 23, 287-294. 2009.
HARDY, W.D. JR., OLD, L. J., HESS, P. W., ESSEX, M., et al. Horizontal transmission of feline leukemia virus. Nature. 244, 266. 1973.
HARDY, W.D.. JR., HESS. P.W., MACEWEN, E.G., MCCLELLAND, A.J.. ZUCKERMAN. E.E., ESSEX. M., COTTER, S.M., JARRETT. 0.. Biology of feline leukemia virus in the natural environment. Cancer Research. 36. 582-588. 1976.
HARTMANN, K. Clinical aspects of feline retroviruses: a review. Viruses 4, 2684–2710. 2012.
HEDDLE, J.A. A rapid in vivo test for chromosome damage. Mutation Research. 18, 187– 192. 1973.
HOOVER, E.A. & MULLINS, J.I. Feline leukemia virus infection and diseases. Journal of the American Veterinary Medical Association 199, 1287–1297. 1991.
HSU, T.C. & REARDEN, H.H. Further Karyological Studies on Felidae. Chromosoma (Berl.), v.16. p.365371, 1965.
HUTSON, C.A., RIDEOUT, B.A., PEDERSEN, N.C. Neoplasia associated with feline immunodeficiency virus infection in cats of Southern California. Journal of the American Veterinary Medical Association 199. 1357-1362. 1991.
JAFFE, E.S., HARRIS, N.L., STEIN, H. & VARDIMAN, J.W. Tumours of Haematopoietic and Lymphoid Tissues (Lyon, IARC Press). 2001.
JOHNSON, W.E., SLATTERY, J.P., EIZIRIK, E. et al. Disparate phylogeographic patterns of molecular genetic variation in four closely related South American small cat species. Molecular Ecology, v.8, p.79-94, 1999.
JONKERS, J. & BERNS, A. Retroviral insertional mutagenesis as a strategy to identify cancer genes. Biochimica et Biophysica Acta 1287, 29–57. 1996.
JORDE, L.B., CAREY, J.C., BAMSHAD, M.J. & WHITE, R.L. 2000. Genética Médica. 2 ed. Rio de Janeiro: Guanabara Koogan.
KIMURA, M., UMEGAKI, K., HIGUCHI, M., THOMAS, P. & FENECH, M. MTHFR C677T polymorphism, folic acid and riboflavin are important determinants of genome stability in cultured human lymphocytes. Journal of Nutrition. 134, 48–56. 2004.
KLEIN, A. DE, KESSEL A. G. VAN & GROSVELD G. A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia. Nature 300, 765. 1982. KLEIN, G. The role of gene dosage and genetic transpositions in carcinogenesis. Nature 294, 313. 1981.
KNUDSON, JR., A.G. Hereditary cancer, oncogenes, and antioncogenes. Cancer Research. 45, 1437–1443. 1985.
LEVESQUE, K.S., BONHAM, L., LEVY, L.S. flvi-1, a common integration domain of feline leukemia virus in naturally occurring lymphomas of a particular type. Journal of Virology. 64, 3455–3462. 1990.
LEVESQUE, K.S., MATTEI, M.G., LEVY, L.S. Evolutionary conservation and chro- mosomal localization of flvi-1. Oncogene 6, 1377–1379. 1991.
LEVY, L.S., LOBELLE-RICH, P.A., OVERBAUGH, J. flvi-2, a target of retroviral inser- tional mutagenesis in feline thymic lymphosarcomas, encodes bmi-1. Oncogene 8, 1833– 1838. 1993.
LI, J., SHEN, H., HIMMEL, K.L., DUPUY, A.J., LARGAESPADA, D.A., NAKAMURA, T., SHAUGH- NESSY JR., J.D., JENKINS, N.A., COPELAND, N.G. LEUKAEMIA disease genes: large-scale cloning and pathway predictions. Nature Genetics. 23, 348–353. 1999.
LOUWERENS, M., LONDON, C.A., PEDERSEN, N.C. & LYONS, L.A. Feline lymphoma in the post-feline leukemia virus era. Journal of Veterinary Internal Medicine. May- Jun;19(3):329-35. 2005.
MAYR, B. & ORTNER W. Loss of chromosome B2-material in three cats of feline mammary tumours. Research in Veterinary Science. 59, 61-63. 1995.
MAYR, B., WEGSCHEIDER, H., REIFINGER, M., et al. Cytogenetic Alterations in Four Feline SoftTissue Tumours. Veterinary Research Communications, v.22, p.21-29, 1998. MAYR, B., WINKLER, G., SCHAFFNER, G., REIFINGER, M. & BREM, G. Short communication: N-ras mutation in a feline lymphoma. Low frequency of N-ras mutations in a series of feline, canine and bovine lymphomas. The Veterinary Journal, 163, 326-328. 2002.
MICHEL, K.E. & SORENMO, K.U. Nutritional status of cats with cancer: nutritional evaluation and recommendations. 2008. In: P. PIBOT, V. BIOURGE & D. ELLIOTT (Eds.), Encyclopedia of Feline Clinical Nutrition.
MIURA, T., SHIBUYA, M., TSUJIMOTO, H., FUKASAWA, M., HAYAMI, M. Molecular cloning of a feline leukemia provirus integrated adjacent to the c-myc gene in a feline T-cell leukemia cell line and the unique structure of its long terminal repeat. Virology 169, 458–461. 1989.
MIURA, T., TSUJIMOTO, H., FUKASAWA, M., KODAMA, T., et al. Structural abnormality and over-expression of the myc gene in feline leukemias. International Journal of Cancer. 40, 564. 1987.
MUNDAY, J.S., DUNOWSKA, M., HILLS, S.F., LAURIE, R.E. Genomic characterization of Felis catus papillomavirus-3: A novel papillomavirus detected in a feline Bowenoid in situ carcinoma. Veterinary Microbiology 165, 319–325. 2013.
NEIL, J.C., FULTON, R., RIGBY, M., HOOVER, E.A. Feline leukemia virus: generation of pathogenic and oncogenic variants. Current Topics in Microbiology and Immunology, 171, 67-93. 1991.
NEIL, J.C., HUGHES, D., MCFARLANE, R., WILKIE, N.M., ONIONS, D.E., LEES, G., JARRETT, O. Transduction and rearrangement of the myc gene by feline leukaemia virus in naturally occurring T-cell leukaemias. Nature 308, 814–820. 1984.
OKUDA, M., UMEDA, A., SAKAI, T., OHASHI, T., et al. Cloning of feline p.53 tumor suppressor gene and its aberration in hematopoietic tumors. International Journal of Cancer 58,602. 1994.
PARKIN, D.M. The global health burden of infection-associated cancers in the year 2002. International Journal of Cancer 118, 3030–3044. 2006.
PONTIER, D., FROMONT, E., COURCHAMP, F., ARTOIS, M., YOCCOZ, G. Retroviruses and sexual size dimorphism in domestic cats (Felis catus). Proceedings Biological Sciences. 265, 167– 173. 1998.
REZANKA, L.J., ROJKO, J.L., NEIL, J.C. Feline leukemia virus- pathogenesis of neoplastic disease. Cancer Investigation 10, 371–389. 1992.
RIPPS, C. S. & HURVITZ, A. I. Myeloproliferative disorder in two cats: cytogenetic studies. American Journal of Veterinary Research. 32, 93. 1971.
RITT M.G. Epidemiology of Hematopoietic Neoplasia, p.453-458. In: WEISS & WARDROP K.J. Schalm’s Veterinary Hematology. 2010. 6th ed. Wiley-Blackwell. Ames.
ROCHA, J.C.C. & SILVA, S.N. Oncogenética. In: COELHO FRG, KOWALSKI LP. Bases da Oncologia. 2. ed. São Paulo: TECMEDD; 2003: p. 423-32.
SANTANA, A. E. Oncologia em cães e gatos, IN: DALECK, C. R.; NARDI, A. B.; RODASKI, S. 1ª Edição. São Paulo: Roca, 2009.
SCHMIDT-KÜNTZEL, A., NELSON, G., DAVID, V.A. et al. A Domestic cat X Chromosome Linkage Map and the Sex-Linked orange Locus: Mapping of orange, Multiple Origins and Epistasis Over nonagouti. Genetics, v.181, p.1415-1425, 2009.
SCHNEIDE, R., FRYE, F.L., TAYLOR, D.O.N., DORN, C.R. A household cluster of malignant lymphoma. Cancer Research 27, 1316–1322. 1967.
SHELTON, G.H., GRANT, C.K., COTTER, S.M., GARDNER, M.B., HARDY, W.D., DIGIACOMO, R.F. Feline immunodeficiency virus and feline leukemia-virus infections and their relationships to lymphoid malignancies in cats – a retrospective study (1968–1988). Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 3, 623– 630. 1990.
SHIMIZU, N., ITOH, N., UTIYAMA, H. & WAHL, G.M. Selective entrapment of extrachromosomally amplified DNA by nuclear budding and micronucleation during S phase. Journal of Cell Biology. 140, 1307–1320. 1998.
SHIMIZU, N., SHIMUARA, T. & TANAKA, T. Selective elimination of acentric double minutes from cancer cells through the extrusion of micronuclei. Mutation Research. 448, 81–90. 2000.
SHIMIZU, N., SHINGAKI, K., KANEKO-SASAGURI, Y., HASHIZUME, T. & KANDA, T. When, where and how the bridge breaks: anaphase bridge breakage plays a crucial role in gene amplification and HSR generation. Experimental Cell Research. 302, 233–243. 2005. TOGNI, M., CURTIS, A., KOMMERS, G.D., IRIGOYEN, L.F., FIGHERA, R.A. Causas de morte e razões para eutanásia em gatos na Região Central do Rio Grande do Sul (1964-2013).
2016. 80f. Tese de doutorado (Patologia Veterinária) – Programa de Pós-graduação em Medicina Veterinária, Universidade Federal de Santa Maria.
TSATSANIS, C., FULTON, R., NISHIGAKI, K., TSUJIMOTO, H., et al. Genetic determinants of feline leukemia virus- induced lymphoid tumors: patterns of proviral insertion and gene rearrangement. Journal of Virology. 68, 8296. 1994.
TSUJIMOTO, H., FULTON, R., NISHIGAKI, K., MATSUMOTO, Y., HASEGAWA, A., TSUJIMOTO, A., CEVARIO, S., O’BRIEN, S.J., TERRY, A., ONIONS, D., et al. A common proviral inte- gration region, fit-1, in T-cell tumors induced by myc-containing feline leukemia viruses. Virology. 196, 845–848. 1993.
TSUJIMOTO, Y., FINGER, L. R., YUNIS, J., NOWELL, P. C., et al. Cloning of the chromosome breakpoint of neoplas- tic B cell with the t(14;18) chromosome translocation. Science. 226, 1097. 1984.
VAIL, D. M. Manual Sanders: Clínica de pequenos animais. IN: BIRCHARD, S. J.; SHERDING, R. G. 2008. 3ª Edição. São Paulo: Roca.
VAIL, D.M. Feline lymphoma and leukemia. In: WITHROW, S.J., VAIL, D.M., PAGE, R.L. (Eds). Withrow and MacEwen’s. Small animal clinical oncology. (5th ed.). (p. 638-653). Missouri: Saunders Elsevier. 2013.
WALKER, D. Diagnóstico citológico e hematologia de cães e gatos, IN: COWELL, R. L; TYLER, R. D.; MEINKOTH, J. H.; DENICOLA, D. B. 2009. 3ª Edição. São Paulo: Med. Vet.
WEEDEN, A.L., TAYLOR, K.R., TERRELL, S.P., GALLAGHER, A.E., WAMSLEY, H.L. Suspected myelodysplastic/myeloproliferative neoplasm in a feline leukemia virus-negative cat. Veterinary Clinical Pathology, 45/4, 584–593. 2016.
WILSON, H.M. Feline alimentary lymphoma: demystifying the enigma. Topics in Companion Animal Medicine, 23(4), 177-184. 2008.
WOZENCRAFT, W.C. Order Carnivora. In: WILSON, D.E., REEDER, D.M. (Eds.). Mammal Species of the World. A taxonomic and geographic reference. 3.ed. Baltimore: The Johns Hopkins University Press, 2005. p.532-545.
YAMAMOTO, J.K., SPARGER, E., HO E.W., ANDERSEN, P.R., O’CONNOR, P., MANDELL, C.P., LOWENSTINE, L., MUNN, R., PEDERSEN, N.C. The pathogenesis of experimentally induced feline immunodeficiency virus infection in cats. American Journal of Veterinary Research. 49, 1246-1258. 1988.
YANG, F., MILNE, B.S., SCHELLING, C., DOLF, G., SCHLÄPFER, J., SWITONSKI, M., LADON, D., PIENKOWSKA, A., BOSMA, A.A., SARGAN, D.R. & FERGUSON- SMITH, M.A. Chromosome identification and assignment of DNA clones in the dog using a red fox and dog comparative map. Chromosomic Research, v. 8, p. 93-110. 2000.
YANG, F.W., IIJIMA, K., TSUJIMOTOT, H., TAMURAT, Y. & HIGURASHI, M. Chromosomal translocations in two feline t-cell lymphomas. Leukemia Research. Vol. 19, No. 11, pp. 857-860. 1995.