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(American Journal of Pathology. 2001;158:1599-1603.)
© 2001 American Society for Investigative Pathology

Short Communications

Translocation t(4;14)(p16.3;q32) Is a Recurrent Genetic Lesion in Primary Amyloidosis

Vittorio Perfetti^*, Addolorata M. L. Coluccia^*, Daniela Intini, Ursula Malgeri, Maurizio Colli Vignarelli^*, Simona Casarini^*, Giampaolo Merlini and Antonino Neri

From the Department of Internal Medicine,^*
Internal Medicine and Medical Oncology, and the Department of Biochemistry,
Biotechnology Research Laboratories, Instituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, University of Pavia, Pavia; and the Hematology Service,
Instituto di Ricovero e Cura a Caraterre Scientifico Ospedale Policlinico, Milan, Italy

Primary amyloidosis is a fatal disorder characterized by low numbers of clonal plasma cells in the bone marrow and the systemic deposition of light chain fragments in the form of amyloid. The molecular pathobiology of amyloidosis is primarily unknown. Recently, a novel karyotypically undetectable t(4;14)(p16.3;q32) translocation has been identified in 20% of multiple myeloma patients. The translocation leads to the apparent deregulation of two genes located on 4p16.3, the fibroblast growth-factor receptor 3 (FGFR3), and the putative transcription factor multiple myeloma SET domain (MMSET), and to the generation of IGH/MMSET hybrid transcripts. In this study, we investigated the presence of the t(4;14) translocation in 42 AL patients using a reverse transcriptase-polymerase chain reaction assay for the detection of IGH/MMSET transcripts. Chimeric transcripts were found in six patients (14%) and were consistent with a 4p16.3 breakpoint involving intron 3 and juxtaposing IGH regions to exon 4. In three of these cases, hybrid transcripts juxtaposing IGH regions to exon 5 were also observed and were probably the result of an alternative splicing skipping exon 4. Because all of the fusion transcripts (six of six) excluded exon 3, the first translated MMSET exon, only putative 5' truncated MMSET proteins could be generated. In conclusion, our results demonstrate that the t(4;14)(p16.3;q32) translocation is a recurrent genetic lesion in primary amyloidosis.

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