Incidence and subtype specificity of AP12-MALT1 fusion translocations in extranodal, nodal, and splenic marginal zone lymphomas

The t(11;18)(q21;q21) is thought to represent an important primary event in the development of marginal zone lymphomas, although an accurate estimatio n of the frequency and distribution of this genetic alteration among nodal, splenic, and extranodal marginal zone lymphoma types has yet to be determi ned. Recently, molecular genetic studies have shown that this translocation results in the fusion of the API2 gene on chromosome 11 and a novel gem te rmed MALT1 on chromosome 18, To investigate the incidence of API2-MALTI fus ion transcripts among marginal zone lymphomas and to determine possible mar ginal zone lymphoma subtype associations, we used reverse transcriptase-pol ymerase chain reaction to analyze RNAs extracted from frozen tissue samples of 99 marginal zone lymphomas, Fifty-seven involved diverse extranodal sit es including 14 stomach, II lung, 7 orbit, 7 parotid, 5 thyroid, 5 lacrimal gland, 3 small intestine, 2 large intestine, I kidney, 1 paraspinal region and 1 skin. Twenty-one primary splenic and twenty-one primary nodal margin al zone lymphomas were also studied. API2-MALTI fusion transcripts were det ected in 12 of 57 extranodal marginal zone lymphomas (21%), but in none of the nodal or splenic cases. The cDNA sequences of the fusion transcripts we re determined, revealing variation in the coding sequence fusion point for both API2 and MALTI, The findings suggest that t(11;18)(q21;q21) is restric ted to extranodal marginal zone lymphomas and that these tumors have distin ct genetic etiologies in comparison with their splenic and nodal counterpar ts.