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Clinical impact of genetic aberrations in gastric MALT lymphoma: a comprehensive analysis using interphase fluorescence in situ hybridisation
  1. Shotaro Nakamura (sn330{at}cam.ac.uk)
  1. University of Cambridge, United Kingdom
    1. Hongtao Ye
    1. University of Cambridge, United Kingdom
      1. Chris M Bacon
      1. University of Cambridge, United Kingdom
        1. Alison Goatly
        1. University of Cambridge, United Kingdom
          1. Hongxiang Liu
          1. University of Cambridge, United Kingdom
            1. Alison H Banham
            1. University of Oxford, United Kingdom
              1. Roland Ventura
              1. University of Oxford, United Kingdom
                1. Takayuki Matsumoto (matane{at}intmed2.med.kyushu-u.ac.jp)
                1. Kyushu University, Japan
                  1. Mitsuo Iida
                  1. Kyushu University, Japan
                    1. Yutaka Ohji
                    1. Kyushu University, Japan
                      1. Takashi Yao
                      1. Kyushu University, Japan
                        1. Masazumi Tsuneyoshi
                        1. Kyushu University, Japan
                          1. Ming-Qing Du (mqd20{at}cam.ac.uk)
                          1. University of Cambridge, United Kingdom

                            Abstract

                            Background and Aims: There is a need for genetic biomarkers to guide prognosis and management of gastric mucosa-associated lymphoid tissue (MALT) lymphomas. We assessed the incidence and clinical significance of the MALT lymphoma-associated genetic abnormalities t(11;18)/API2-MALT1, t(1;14)/BCL10-IGH, t(14;18)/IGH-MALT1 and t(3;14)/FOXP1-IGH, in gastric MALT lymphomas from Japan.

                            Methods: The presence of translocations and copy number changes involving MALT1, IGH and FOXP1 were assessed in 90 cases of gastric MALT lymphoma using interphase fluorescence in situ hybridisation (FISH). In cases carrying a MALT1 translocation, FISH for API2-MALT1 was performed, while in those carrying an IGH translocation, FISH was performed for BCL10, BCL6, BCL2, c-MYC and/or CCND1. MALT1 and FOXP1 copy number was also evaluated.

                            Results: t(11;18)/API2-MALT1 was detected in 18 (21%) of 87 cases, and was significantly associated with Helicobacter pylori-negativity, resistance to H pylori eradication, and Bcl10 nuclear expression. Four (6%) of 68 cases carried a translocation involving IGH and FOXP1 (n=1), BCL2 (n=1) or an unknown partner (n=2). Neither t(1;14)/BCL10-IGH nor t(14;18)/IGH-MALT1 was detected. Extra copies of MALT1 and FOXP1 were detected in 18 of 71 cases (25%) and 10 of 59 cases (17%), respectively. The presence of extra copies of MALT1 was significantly associated with progression or relapse of lymphoma, and was an independent adverse prognostic factor for event-free survival as determined by multivariate analysis.

                            Conclusions: t(11;18)/API2-MALT1 is frequent, while IGH-involved translocations are rare in gastric MALT lymphoma in Japan. The presence of extra copies of MALT1, often suggestive of partial or complete trisomy 18, is a frequent genetic aberration in gastric MALT lymphoma, which appears to predict adverse clinical behaviour.

                            • FISH
                            • MALT lymphoma
                            • chromosome translocation
                            • gastric lymphoma

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