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MALT lymphoma: t(11;18), t(1;14) and t(14;18) and their role in pathogenesis, diagnosis, prognosis and treatment.

Ye, H; (2002) MALT lymphoma: t(11;18), t(1;14) and t(14;18) and their role in pathogenesis, diagnosis, prognosis and treatment. Doctoral thesis , University of London. Green open access

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Abstract

MALT lymphoma is specifically associated with t(11; 18)(q2l; q2l), t(1; 14)(p22q; 32) and t(14;1 8)(q32q; 2l). t(11; 18)(q2l; q2l) fuses the N-terminal of the API2 gene to the Cterminal of the MALT1 gene and generates a functional AP12-MALTI fusion product. t(1; 14)(p22q; 32) and t(14; 18)(q32q; 2l) bring the BCLIO and MALT1 gene respectively to the IgH locus and deregulate their expression. The oncogenic activity of the three independent chromosomal translocations is linked by the physiological role of BCLIO and MALTI. in antigen receptor mediated NFKB activation. In this thesis, immunohistochemical and molecular genetic methods have been developed and used to investigate the frequency of these translocations in MALT lymphomas of various sites and their role in the pathogenesis, diagnosis, prognosis and treatment of this malignancy. t(l 1; 1 8)(q2 I; q2 1) was detected by RT-PCR of the AP12-MALT I fusion transcript and was found most frequently in MALT lymphomas from the lung (38%) and stomach (24%), moderately in those from the ocular adnexae (16%), but rarely in those from the salivary gland (M), thyroid, skin, and other rare sites. The translocation was not seen in the preceding diseases associated with the development of MALT lymphoma including H. pylori associated gastritis, lymphoepithelial sialadenitis and Hashimoto's thyroiditis, nor in other subtypes of non-Hodgkin's lymphomas. In gastric MALT lymphoma, t(11; 18)(q2l; q2l) was significantly associated with advanced cases and was a reliable marker for those not responding to H. pylori eradication including cases at stage IE. t(1; 14)(p22q; 32) positive MALT lymphoma was characterised by strong BCLIO nuclear expression in contrast to the cytoplasmic expression of the protein in normal B-cells. Moderate BCLIO nuclear expression was seen in t(1; 14)(p22q; 32) negative MALT lymphomas including all those with t(11; 18)(q2l; q2l) and up to 20% of cases without t(11; 18)(q2l; q2l). Based on BCLIO immunohistochemstry followed by interphase FISH, t(1; 14)(p22q; 32) was found in MALT lymphomas from the lung (12%) and stomach( 5%), but not in those from the ocular adnexae, salivary gland, thyroid and skin. In gastric MALT lymphoma,t (1; 14)(p22q; 32) positive cases did not respond to H. pylori eradication. t(14;1 8)(q32q; 2l) positive MALT lymphoma was characterised by strong homogeneous cytoplasmic expression of both MALTI. and BCLIO. In MALT lymphomas without t(14;1 8)(q32q; 2l) including those with t(1; 14)(p22q; 32) or t(11; 18)(q2l; q2l), MALTI expression was generally weak or negative. Based on MALTI and BCLIO immunohistochernistry followed by interphase FISH, t(14; 18)(q32q; 2l) was found in MALT lymphomas of the lung (6%), ocular adnexae (7%) and liver (17%) but not in those from the stomach, salivary gland, thyroid and skin. t(11;1 8)(q21q; 2l), t(1; 14)(p22q; 32) and t(14; 18)(q32q; 21) were variably involved in MALT lymphoma of different sites. Detection of these translocations has significant implications in diagnosis and prognosis of MALT lymphoma.

Type: Thesis (Doctoral)
Title: MALT lymphoma: t(11;18), t(1;14) and t(14;18) and their role in pathogenesis, diagnosis, prognosis and treatment.
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by British Library EThOS. The orginal pages 213 to 251 have been excluded due to third party copyright.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
URI: http://discovery.ucl.ac.uk/id/eprint/1383807
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