engleski

Molecular detection and clinics of IgH/MMSET-t(4 ; 14)(p16 ; q32)in multiple myeloma.

Chromosomal translocation t(4 ; 14)(4p16 ; 14q32) leads to overexpression of FGFR3 and WHSC1/MMSET genes (4p16)due to the activity of regulatory elements of IgH gene(14q32). IgH/MMSET rearrangement is an adverse prognostic factor for myeloma and diagnostically molecular detection of the fusion transcript by an RT-PCR test confi rms the existence of translocation. We used nested RT-PCR assay for IgH-MMSET detection (after Malgeri et al. Cancer Res 2000 ; 60:4058) in a group of 64 patients with MM diagnosed at our institutions over the last fi ve years. We found 10 (15, 6%) patients with IgH-MMSET transcripts in BM or PB. Mean age was 62, 2 years, paraprotein was IgA in 3, IgG in 6 and light chains kappa in one. Five positive patients died of MM in the period of 2 years after diagnosis, one of plasma cell leukemia. One further patient died after transformation to MDS. Three patients are in the stable phase of disease and one shows progression after 20 years of MM history. In our IgH/MMSET-positive patients we noted an increased predisposition to extramedulary sites or the occurrence of localized bone destructive and soft tissue invading of plasmocytoma. Molecularly, 3/10 fusion transcripts were MB4-1 type. For one of them we confi rmed the break in exon 3 of MMSET by sequencing. Two thirds ofmolecular isoforms were of MB4-2 type. In conclusion, the prevalence of 15, 6% IgH/MMSET in our so far tested patients corresponds to the expected frequency for this genetic lesion in MM. Distribution of fusion gene molecular isoforms is in favor of MB4-2 type. Clinically, also presentation of locally aggressive and extramedulary t(4 ; 14)+ myeloma tumors could be expected.

IgH/MMSET; T(4; 14)(4P16; 14Q32); molecular detection; multiple myeloma

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