EXON SKIPPING WITHOUT SPLICE-SITE MUTATION ACCOUNTING FOR ABNORMAL IMMUNOGLOBULIN-CHAINS IN NONSECRETORY HUMAN MYELOMA

The proliferating plasma cells of patient COM with nonsecretory myelom a synthesized truncated 42 kDa gamma1 chains made of a complete consta nt region but devoid of variable domain. In the absence of light chain expression, the shortened gamma chains were retained intracellularly and were subsequently degraded within 12 h. COM neoplastic plasma cell s contained short gamma1 heavy chain transcripts in which the leader p eptide exon was directly joined to the CH1 exon using the regular spli ce sites. However, study of the productive gamma gene showed that the skipped variable exon was bounded by normal splicing signals and that the adjacent intron organization was not altered. Since this unusual s plicing pattern was maintained when COM gamma gene was transfected in murine plasmocytoma cells, exon skipping possibly relates to the modif ied structure of COM variable region. The latter showed a 2-base pair deletion introducing a translation frameshift in the V(H) region and a DNA insertion at the V(H)-DJ(H) junction consisting in a perfect dupl ication of the first 54 nucleotides of the recombined DJ(H) segment.Th e lack of light chain production by COM cells was explained by alterat ions of the variable region of the rearranged kappa gene leading to ab normally spliced transcripts.