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Detection of chromosomal abnormalities by G-banding and prognostic impact in follicular lymphoma in the rituximab era

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Abstract

Disease-specific cytogenetic abnormalities involving BCL2 gene rearrangement frequently co-exist with other cytogenetic abnormalities, contributing to disease progression in follicular lymphoma (FL). In the present study, we retrospectively investigated the prognostic impact of BCL2-unrelated cytogenetic abnormalities in FL. Of 139 consecutively diagnosed patients with FL at two independent institutes, metaphase spreads of tumor cells were obtained for use in G-banding analysis in 77 patients. The recurrent additional cytogenetic abnormalities included chromosome gains +5 (n = 8), +7 (n = 16), +12 (n = 10), and +X (n = 12), and losses −8 (n = 7), −13 (n = 12) −15 (n = 7), and 6q− (n = 7). While −15 was associated with shorter progression-free survival (PFS) in all 77 analyzed patients with evaluable G-banding results (p = 0.04), this negative impact was not evident in 42 patients treated using an R-CHOP-like regimen as first-line treatment. By contrast, 6q− was predictive for shorter PFS in patients who were initially treated with R-CHOP-like regimens without maintenance therapy (p < 0.01), while this negative impact was not evident in all 77 patients with evaluable G-banding results. These results suggest the presence of a molecular region in chromosome 6q that is responsible for the shorter PFS following R-CHOP-like chemotherapy.

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References

  1. Wagner-Johnston ND, Link BK, Byrtek M, Dawson KL, Hainsworth J, Flowers CR, et al. Outcomes of transformed follicular lymphoma in the modern era: a report from the National LymphoCare Study (NLCS). Blood. 2015;126:851–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Limpens J, Stad R, Vos C, de Vlaam C, de Jong D, van Ommen GJ, et al. Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals. Blood. 1995;85:2528–36.

    CAS  PubMed  Google Scholar 

  3. Dolken G, Illerhaus G, Hirt C, Mertelsmann R. BCL-2/JH rearrangements in circulating B cells of healthy blood donors and patients with nonmalignant diseases. J Clin Oncol. 1996;14:1333–44.

    Article  CAS  PubMed  Google Scholar 

  4. Jegalian AG, Eberle FC, Pack SD, Mirvis M, Raffeld M, Pittaluga S, et al. Follicular lymphoma in situ: clinical implications and comparisons with partial involvement by follicular lymphoma. Blood. 2011;118:2976–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kridel R, Sehn LH, Gascoyne RD. Pathogenesis of follicular lymphoma. J Clin Invest. 2012;122:3424–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Green MR, Kihira S, Liu CL, Nair RV, Salari R, Gentles AJ, et al. Mutations in early follicular lymphoma progenitors are associated with suppressed antigen presentation. Proc Natl Acad Sci USA. 2015;112:E1116–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011;476:298–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Okosun J, Bodor C, Wang J, Araf S, Yang CY, Pan C, et al. Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Nat Genet. 2014;46:176–81.

    Article  CAS  PubMed  Google Scholar 

  9. Cheung KJ, Shah SP, Steidl C, Johnson N, Relander T, Telenius A, et al. Genome-wide profiling of follicular lymphoma by array comparative genomic hybridization reveals prognostically significant DNA copy number imbalances. Blood. 2009;113:137–48.

    Article  CAS  PubMed  Google Scholar 

  10. Bouska A, McKeithan TW, Deffenbacher KE, Lachel C, Wright GW, Iqbal J, et al. Genome-wide copy-number analyses reveal genomic abnormalities involved in transformation of follicular lymphoma. Blood. 2014;123:1681–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Asmann YW, Maurer MJ, Wang C, Sarangi V, Ansell SM, Feldman AL, et al. Genetic diversity of newly diagnosed follicular lymphoma. Blood Cancer J. 2014;4:e256.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tilly H, Rossi A, Stamatoullas A, Lenormand B, Bigorgne C, Kunlin A, et al. Prognostic value of chromosomal abnormalities in follicular lymphoma. Blood. 1994;84:1043–9.

    CAS  PubMed  Google Scholar 

  13. James GK, Horsman D, Connors JM, Klasa R, Wilson K, Argatoff L, et al. Clinicopathological analysis of follicular lymphoma with a polyploid karyotype. Leuk Lymphoma. 1998;28:383–9.

    Article  CAS  PubMed  Google Scholar 

  14. Horsman DE, Connors JM, Pantzar T, Gascoyne RD. Analysis of secondary chromosomal alterations in 165 cases of follicular lymphoma with t(14;18). Genes Chromosomes Cancer. 2001;30:375–82.

    Article  CAS  PubMed  Google Scholar 

  15. Mohamed AN, Palutke M, Eisenberg L, Al-Katib A. Chromosomal analyses of 52 cases of follicular lymphoma with t(14;18), including blastic/blastoid variant. Cancer Genet Cytogenet. 2001;126:45–51.

    Article  CAS  PubMed  Google Scholar 

  16. Fan Y-S, Rizkalla K. Comprehensive cytogenetic analysis including multicolor spectral karyoty** and interphase fluorescence in situ hybridization in lymphoma diagnosis. Cancer Genet Cytogenet. 2003;143:73–9.

    Article  CAS  PubMed  Google Scholar 

  17. Viardot A, Barth TF, Moller P, Dohner H, Bentz M. Cytogenetic evolution of follicular lymphoma. Semin Cancer Biol. 2003;13:183–90.

    Article  PubMed  Google Scholar 

  18. Hoglund M, Sehn L, Connors JM, Gascoyne RD, Siebert R, Sall T, et al. Identification of cytogenetic subgroups and karyotypic pathways of clonal evolution in follicular lymphomas. Genes Chromosomes Cancer. 2004;39:195–204.

    Article  PubMed  Google Scholar 

  19. Nanjangud G, Rao PH, Teruya-Feldstein J, Donnelly G, Qin J, Mehra S, et al. Molecular cytogenetic analysis of follicular lymphoma (FL) provides detailed characterization of chromosomal instability associated with the t(14;18)(q32;q21) positive and negative subsets and histologic progression. Cytogenet Genome Res. 2007;118:337–44.

    Article  CAS  PubMed  Google Scholar 

  20. d’Amore F, Chan E, Iqbal J, Geng H, Young K, **ao L, et al. Clonal evolution in t(14;18)-positive follicular lymphoma, evidence for multiple common pathways, and frequent parallel clonal evolution. Clin Cancer Res. 2008;14:7180–7.

    Article  PubMed  Google Scholar 

  21. Johnson NA, Al-Tourah A, Brown CJ, Connors JM, Gascoyne RD, Horsman DE. Prognostic significance of secondary cytogenetic alterations in follicular lymphomas. Genes Chromosomes Cancer. 2008;47:1038–48.

    Article  CAS  PubMed  Google Scholar 

  22. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2008.

    Google Scholar 

  23. Solal-Celigny P, Roy P, Colombat P, White J, Armitage JO, Arranz-Saez R, et al. Follicular lymphoma international prognostic index. Blood. 2004;104:1258–65.

    Article  CAS  PubMed  Google Scholar 

  24. Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, et al. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol. 2009;27:4555–62.

    Article  PubMed  Google Scholar 

  25. Shaffer L, McGowan-Jordan J, Shmid M. An international system for human cytogenetic nomenclature, (S Karger, Basel 2013). ISCN (2013). 2013.

  26. Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005;106:3725–32.

    Article  CAS  PubMed  Google Scholar 

  27. Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, et al. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013;31:1506–13.

    Article  CAS  PubMed  Google Scholar 

  28. Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013;381:1203–10.

    Article  CAS  PubMed  Google Scholar 

  29. Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011;377:42–51.

    Article  CAS  PubMed  Google Scholar 

  30. Igarashi T, Ogura M, Itoh K, Taniwaki M, Ando K, Kuroda Y, et al. Japanese phase II study of rituximab maintenance for untreated indolent B-cell non-Hodgkin lymphoma with high tumor burden. Int J Hematol. 2016;104:700–8.

    Article  CAS  PubMed  Google Scholar 

  31. Cheung KJ, Johnson NA, Affleck JG, Severson T, Steidl C, Ben-Neriah S, et al. Acquired TNFRSF14 mutations in follicular lymphoma are associated with worse prognosis. Cancer Res. 2010;70:9166–74.

    Article  CAS  PubMed  Google Scholar 

  32. Honma K, Tsuzuki S, Nakagawa M, Tagawa H, Nakamura S, Morishima Y, et al. TNFAIP3/A20 functions as a novel tumor suppressor gene in several subtypes of non-Hodgkin lymphomas. Blood. 2009;114:2467–75.

    Article  CAS  PubMed  Google Scholar 

  33. Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K, et al. Frequent inactivation of A20 in B-cell lymphomas. Nature. 2009;459:712–6.

    Article  CAS  PubMed  Google Scholar 

  34. Dong G, Chanudet E, Zeng N, Appert A, Chen YW, Au WY, et al. A20, ABIN-1/2, and CARD11 mutations and their prognostic value in gastrointestinal diffuse large B-cell lymphoma. Clin Cancer Res. 2011;17:1440–51.

    Article  CAS  PubMed  Google Scholar 

  35. Hideshima T, Ikeda H, Chauhan D, Okawa Y, Raje N, Podar K, et al. Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells. Blood. 2009;114:1046–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Mrs. N. Inada and Mrs. T. Ikawa for their technical support. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT KAKENHI 16K09856) (MT), and by a grant from the Takeda Science Foundation (JK).

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Taku Tsukamoto, Miki Kiyota, Shotaro Tatekawa, Yoshiaki Chinen, Hisao Nagoshi, Shinsuke Mizutani, Yuji Shimura, Mio Yamamoto-Sugitani, Tsutomu Kobayashi, Shigeo Horiike, Masafumi Taniwaki & Junya Kuroda

  2. Department of Hematology, Matsushita Memorial Hospital, Osaka, Japan

    Miki Kiyota

  3. Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan

    Eri Kawata & Nobuhiko Uoshima

  4. Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Satoru Yasukawa & Akio Yanagisawa

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  1. Taku Tsukamoto
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Tsukamoto, T., Kiyota, M., Kawata, E. et al. Detection of chromosomal abnormalities by G-banding and prognostic impact in follicular lymphoma in the rituximab era. Int J Hematol 105, 658–667 (2017). https://doi.org/10.1007/s12185-016-2166-0

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