Molecular alterations of IL-6R, lck and c-myc genes in transforming monoclonal gammopathies of undetermined significance.
We studied the molecular alterations of IL-6R, lck and c-myc genes in the tumour cells of 50 patients with multiple myeloma (MM) and 20 patients with monoclonal gammopathies of undetermined significance (MGUS). Southern blot analysis revealed a 5.3 kb IL-6R amplified band by digestion with EcoRI and HindIII in three MGUS patients, but no IL-6R gene alteration was found in MM patients. BamHI digestion revealed a 6.2 kb rearranged band of the lck gene in two MGUS patients with IL-6R amplification. In one MGUS patient we detected a rearrangement upstream of the lck coding region. Myc rearrangement was observed in three MM and two MGUS patients who showed coexistent lck rearrangement and IL-6R amplification. These molecular alterations were detected in the MGUS patients with an IgA monoclonal component, who showed a rapid progression into aggressive MM. Myc rearrangement seems to be associated with a small group of a clinically aggressive MM at diagnosis, secreting IgA or k light chains. Multiple rearrangements and/or molecular alterations are likely to occur at the time of MGUS-IgA transformation into aggressive MM and myc rearrangement may promote a positive pressure for transformation and progression. MM tumourigenesis remains a heterogenous multistep process involving the deregulation of many genes and gene products.
Gernone
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A
Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari Medical School, Italy.
Dammacco
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F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D015139:Blotting, Southern; D005260:Female; D015321:Gene Rearrangement; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics*; D010265:Paraproteinemias / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*
D015850:Interleukin-6; D011518:Proto-Oncogene Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)