Heterogeneity of the api2-malt1 gene rearrangement in malt-type lymphoma

Heterogeneity of the api2-malt1 gene rearrangement in malt-type lymphoma


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ABSTRACT The translocation t(11;18)(q21;q21), which is the most frequent chromosomal aberration in extranodal marginal zone B cell lymphomas of MALT-type, was characterised in a series of 34


biopsies, including 18 gastric non-Hodgkin's lymphomas (NHL) of MALT-type, six MALT-type NHL of extragastral origin and 10 extranodal large B cell lymphomas (LBL). Based on


fluorescence _in situ_ hybridisation, STS-PCR analysis and screening of genomic PAC libraries, a physical map of contiguous DNA probes on chromosome 11 was constructed containing the


anti-apoptotic genes _API2_ and _API1_ adjacent to the translocation breakpoint. RACE-PCR experiments revealed _MALT1_ the chromosome 18-derived fusion partner of _API2_, which has also been


reported recently by other groups. RT-PCR analysis and DNA sequencing demonstrated the expression of an _API2-MALT1_ fusion transcript in 18/24 gastral and extragastral MALT-type lymphomas.


In none of 10 LBLs was a translocation specific RT-PCR product detected. Five variants of the fusion transcript were identified and in all instances the open reading frame of the fused


portion of the _MALT1_ gene was maintained. The molecular analysis of these variants allowed the design of optimised assays for the diagnosis of the _API2-MALT1_ gene rearrangement. Access


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SIMILAR CONTENT BEING VIEWED BY OTHERS GENOMIC LANDSCAPE OF EPSTEIN–BARR VIRUS-POSITIVE EXTRANODAL MARGINAL ZONE LYMPHOMAS OF MUCOSA-ASSOCIATED LYMPHOID TISSUE Article 24 December 2021 LARGE


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MONITORING OF GASTRIC MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA IN PATIENTS WITH EXTRA COPIES OF THE _MALT1_ GENE Article Open access 29 February 2024 REFERENCES * Isaacson P, Wright DH .


Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma _Cancer_ 1983 52: 1410–1416 Article  CAS  Google Scholar  * Harris NL, Jaffe ES, Stein H, Banks


PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC . A revised European–American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study


Group _Blood_ 1994 84: 1361–1392 CAS  Google Scholar  * Hussell T, Isaacson PG, Crabtree JE, Spencer J . The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated


lymphoid tissue to Helicobacter pylori _Lancet_ 1993 342: 571–574 Article  CAS  Google Scholar  * Greiner A, Marx A, Heesemann J, Leebmann J, Schmausser B, Müller-Hermelink HK . Idiotype


identity in a MALT-type lymphoma and B cells in Helicobacter pylori associated chronic gastritis _Lab Invest_ 1994 70: 572–578 CAS  PubMed  Google Scholar  * Wotherspoon AC, Doglioni C, Diss


TC, Pan L, Moschini A, de Boni M, Isaacson PG . Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori


_Lancet_ 1993 342: 575–577 Article  CAS  Google Scholar  * Bayerdörffer E, Neubauer A, Rudolph B, Thiede C, Lehn N, Eidt S, Stolte M . Regression of primary gastric lymphoma of


mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. MALT Lymphoma Study Group _Lancet_ 1995 345: 1591–1594 Article  Google Scholar  * Auer IA, Gascoyne RD,


Connors JM, Cotter FE, Greiner TC, Sanger WG, Horsman DE . t(11;18)(q21;q21) is the most common translocation in MALT lymphomas _Ann Oncol_ 1997 8: 979–985 Article  CAS  Google Scholar  *


Ott G, Katzenberger T, Greiner A, Kalla J, Rosenwald A, Heinrich U, Ott MM, Müller-Hermelink HK . The t(11;18)(q21;q21) chromosome translocation is a frequent and specific aberration in


low-grade but not high-grade malignant non-Hodgkin's lymphomas of the mucosa-associated lymphoid tissue (MALT-) type _Cancer Res_ 1997 57: 3944–3948 CAS  PubMed  Google Scholar  *


Levine EG, Arthur DC, Machnicki J, Frizzera G, Hurd D, Peterson B, Gajl-Peczalska KJ, Bloomfield CD . Four new recurring translocations in non-Hodgkin lymphoma _Blood_ 1989 74: 1796–1800 CAS


  PubMed  Google Scholar  * Horsman D, Gascoyne R, Klasa R, Coupland R . t(11;18)(q21;q21 _1): a recurring translocation in lymphomas of mucosa-associated lymphoid tissue (MALT)? Genes


Chromosomes Cancer_ 1992 4: 183–187 CAS  PubMed  Google Scholar  * Griffin CA, Zehnbauer BA, Beschorner WE, Ambinder R, Mann R . t(11;18)(q21;q21) is a recurrent chromosome abnormality in


small lymphocytic lymphoma _Genes Chromosomes Cancer_ 1992 4: 153–157 Article  CAS  Google Scholar  * Leroux D, Seite P, Hillion J, Le Marc'hadour F, Pegourie-Bandelier B, Jacob MC,


Larsen CJ, Sotto JJ . t(11;18)(q21;q21) may delineate a spectrum of diffuse small B-cell lymphoma with extranodal involvement _Genes Chromosomes Cancer_ 1993 7: 54–56 Article  CAS  Google


Scholar  * Rosenwald A, Ott G, Stilgenbauer S, Kalla J, Bredt M, Katzenberger T, Greiner A, Ott MM, Gawin B, Döhner H, Müller-Hermelink HK . Exclusive detection of the t(11;18)(q21;q21) in


extranodal marginal zone B cell lymphomas (MZBL) of MALT type in contrast to other MZBL and extranodal large B cell lymphomas _Am J Pathol_ 1999 155: 1817–1821 Article  CAS  Google Scholar 


* Akagi T, Tamura A, Motegi M, Suzuki R, Hosokawa Y, Nakamura S, Morishima Y, Seto M, Taniwaki M . Molecular cytogenetic delineation of the breakpoint at 18q21.1 in low-grade B-cell lymphoma


of mucosa-associated lymphoid tissue _Genes Chromosomes Cancer_ 1999 24: 315–321 Article  CAS  Google Scholar  * Akagi T, Motegi M, Tamura A, Suzuki R, Hosokawa Y, Suzuki H, Ota H, Nakamura


S, Morishima Y, Taniwaki M, Seto M . A novel gene, MALT1 at 18q21, is involved in t(11;18)(q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue _Oncogene_ 1999


18: 5785–5794 Article  CAS  Google Scholar  * Dierlamm J, Baens M, Wlodarska I, Stefanova-Ouzounova M, Hernandez JM, Hossfeld DK, De Wolf-Peeters C, Hagemeijer A, Van den Berghe H, Marynen P


. The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas _Blood_ 1999


93: 3601–3609 CAS  PubMed  Google Scholar  * Morgan JA, Yin Y, Borowsky AD, Kuo F, Nourmand N, Koontz JI, Reynolds C, Soreng L, Griffin CA, Graeme-Cook F, Harris NL, Weisenburger D, Pinkus


GS, Fletcher JA, Sklar J . Breakpoints of the t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma lie within or near the previously undescribed gene MALT1 in chromosome 18


_Cancer Res_ 1999 59: 6205–6213 CAS  PubMed  Google Scholar  * Stoffel A, Rao PH, Louie DC, Krauter K, Liebowitz DN, Koeppen H, Le Beau MM, Chaganti RS . Chromosome 18 breakpoint in


t(11;18)(q21;q21) translocation associated with MALT lymphoma is proximal to BCL2 and distal to DCC _Genes Chromosomes Cancer_ 1999 24: 156–159 Article  CAS  Google Scholar  * Greiner A,


Knörr C, Qin Y, Sebald W, Schimpl A, Banchereau J, Müller-Hermelink HK . Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT-type) require CD40-mediated signaling and


Th2-type cytokines for in vitro growth and differentiation _Am J Pathol_ 1997 150: 1583–1593 CAS  PubMed  PubMed Central  Google Scholar  * Tunnacliffe A, Jones C, Le Paslier D, Todd R,


Cherif D, Birdsall M, Devenish L, Yousry C, Cotter FE, James MR . Localization of Jacobsen syndrome breakpoints on a 40-Mb physical map of distal chromosome 11q _Genome Res_ 1999 9: 44–52


CAS  PubMed  PubMed Central  Google Scholar  * James MR, Richard CW 3rd, Schott JJ, Yousry C, Clark K, Bell J, Terwilliger JD, Hazan J, Dubay C, Vignal A, Agrapart M, Imai T, Nakamura Y,


Polymeropoulos M, Weissenbach J, Cox DR, Lathrop GM . A radiation hybrid map of 506 STS markers spanning human chromosome 11 _Nat Genet_ 1994 8: 70–76 Article  CAS  Google Scholar  * Ioannou


PA, Amemiya CT, Garnes J, Kroisel PM, Shizuya H, Chen C, Batzer MA, de Jong PJ . A new bacteriophage P1-derived vector for the propagation of large human DNA fragments _Nat Genet_ 1994 6:


84–89 Article  CAS  Google Scholar  * Church GM, Gilbert W . Genomic sequencing _Proc Natl Acad Sci USA_ 1984 81: 1991–1995 Article  CAS  Google Scholar  * Parra I, Windle B . High


resolution visual mapping of stretched DNA by fluorescent hybridization _Nat Genet_ 1993 5: 17–21 Article  CAS  Google Scholar  * Rothe M, Pan MG, Henzel WJ, Ayres TM, Goeddel DV . The


TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins _Cell_ 1995 83: 1243–1252 Article  CAS  Google Scholar  * Deveraux QL, Reed JC


. IAP family proteins – suppressors of apoptosis _Genes Dev_ 1999 13: 239–252 Article  CAS  Google Scholar  * Motegi M, Yonezumi M, Suzuki H, Suzuki R, Hosokawa Y, Hosaka S, Kodera Y,


Morishima Y, Nakamura S, Seto M . API2-MALT1 chimeric transcripts involved in mucosa-associated lymphoid tissue type lymphoma predict heterogeneous products _Am J Pathol_ 2000 156: 807–812


Article  CAS  Google Scholar  * Remstein ED, James CD, Kurtin PJ . Incidence and subtype specificity of API2-MALT1 fusion translocations in extranodal, nodal, and splenic marginal zone


lymphomas _Am J Pathol_ 2000 156: 1183–1188 Article  CAS  Google Scholar  * Parsonnet J, Hansen S, Rodriguez L, Gelb AB, Warnke RA, Jellum E, Orentreich N, Vogelman JH, Friedman GD .


Helicobacter pylori infection and gastric lymphoma _New Engl J Med_ 1994 330: 1267–1271 Article  CAS  Google Scholar  * Young SS, Liston P, Xuan JY, McRoberts C, Lefebvre CA, Korneluk RG .


Genomic organization and physical map of the human inhibitors of apoptosis: HIAP1 and HIAP2 _Mamm Genome_ 1999 10: 44–48 Article  CAS  Google Scholar  * Baens M, Maes B, Steyls A, Geboes K,


Marynen P, De Wolf-Peeters C . The product of the t(11;18), an API2-MLT fusion, marks nearly half of gastric MALT type lymphomas without large cell proliferation _Am J Pathol_ 2000 156:


1433–1439 Article  CAS  Google Scholar  * Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC . The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases _EMBO J_ 1997


16: 6914–6925 Article  CAS  Google Scholar  * Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, Srinivasula SM, Alnemri ES, Salvesen GS, Reed JC . IAPs block apoptotic events induced


by caspase-8 and cytochrome c by direct inhibition of distinct caspases _EMBO J_ 1998 17: 2215–2223 Article  CAS  Google Scholar  * Hay BA, Wassarman DA, Rubin GM . Drosophila homologs of


baculovirus inhibitor of apoptosis proteins function to block cell death _Cell_ 1995 83: 1253–1262 Article  CAS  Google Scholar  * Vucic D, Kaiser WJ, Miller LK . A mutational analysis of


the baculovirus inhibitor of apoptosis Op-IAP _J Biol Chem_ 1998 273: 33915–33921 Article  CAS  Google Scholar  * Chan JK, Ng CS, Isaacson PG . Relationship between high-grade lymphoma and


low-grade B-cell mucosa-associated lymphoid tissue lymphoma (MALToma) of the stomach _Am J Pathol_ 1990 136: 1153–1164 CAS  PubMed  PubMed Central  Google Scholar  * Montalban C, Manzanal A,


Castrillo JM, Escribano L, Bellas C . Low grade gastric B-cell MALT lymphoma progressing into high grade lymphoma. Clonal identity of the two stages of the tumour, unusual bone involvement


and leukemic dissemination _Histopathology_ 1995 27: 89–91 Article  CAS  Google Scholar  * Peng H, Du M, Diss TC, Isaacson PG, Pan L . Genetic evidence for a clonal link between low and


high-grade components in gastric MALT B-cell lymphoma _Histopathology_ 1997 30: 425–429 Article  CAS  Google Scholar  * Ott MM, Linke B, Gerhard N, Kneba M, Greiner A, Ott G,


Müller-Hermelink HK . Characterization of clonal B-cell populations in gastric MALT lymphomas and chronic gastritis by means of the polymerase chain reaction _Verh Dtsch Ges Pathol_ 1994 78:


302–304 CAS  PubMed  Google Scholar  * Greiner A, Müller-Hermelink HK . Recent advances in gastric extranodal B-cell lymphoma _Curr Diagn Path_ 1996 3: 91–98 Article  Google Scholar  *


Radaszkiewicz T, Dragosics B, Bauer P . Gastrointestinal malignant lymphomas of the mucosa-associated lymphoid tissue: factors relevant to prognosis _Gastroenterology_ 1992 102: 1628–1638


Article  CAS  Google Scholar  * Knörr C, Amrehn C, Seeberger H, Rosenwald A, Stilgenbauer S, Ott G, Müller Hermelink HK, Greiner A . Expression of costimulatory molecules in low-grade


mucosa-associated lymphoid tissue-type lymphomas _in vivo_ _Am J Pathol_ 1999 155: 2019–2027 Article  Google Scholar  Download references ACKNOWLEDGEMENTS The human PAC library was created


at Roswell Park Cancer Institute by Panos A Ioannou (RPCI-1), Chira Chen and Baohui Zhao (RPCI-3), and Baohui Zhao (RPCI-4 and 5). High density filters and clones were kindly provided by the


Resource Center/Primary Database of the German Human Genome Project, Berlin, Germany. Michael James kindly provided information on the physical map of the YACs. The authors gratefully thank


Simone Schindelmann, Sandra Weitz and Ralf Klären for their technical assistance. Finally, we also acknowledge Peter Marynen for open discussion. This work was supported by grants from the


Deutsche Forschungsgemeinschaft (Ka 1449/1–1) and the Sander-Stiftung (94.025.2 and 98.086.1) AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * ‘Organisation komplexer Genome’, Deutsches


Krebsforschungszentrum, Heidelberg, Germany J Kalla, C Schaffner, S Wolf & P Lichter * Innere Medizin III, Universität Ulm, Ulm, Germany S Stilgenbauer & H Döhner * Pathologisches


Institut der Universität Würzburg, Würzburg, Germany G Ott, A Greiner, A Rosenwald & HK Müller-Hermelink Authors * J Kalla View author publications You can also search for this author


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and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kalla, J., Stilgenbauer, S., Schaffner, C. _et al._ Heterogeneity of the _API2-MALT1_ gene rearrangement in MALT-type lymphoma.


_Leukemia_ 14, 1967–1974 (2000). https://doi.org/10.1038/sj.leu.2401918 Download citation * Received: 22 May 2000 * Accepted: 05 July 2000 * Published: 02 November 2000 * Issue Date: 01


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shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * MALT-type lymphoma * extranodal


large B cell lymphoma * t(11 * 18)(q21 * q21) * _API2_ * _MALT1_