Concurrent activation of a novel putative transforming gene, myeov, and cyclin D1 in a subset of multiple myeloma cell lines with t(11;14)(q13;q32).
Through the application of the NIH/3T3 tumorigenicity assay to DNA from a gastric carcinoma, we have identified a novel transforming gene, designated myeov (myeloma overexpressed gene in a subset of t[11;14]-positive multiple myelomas). Sequence analyses did not reveal any homology with sequences present in the GenBank, except the deduced protein structure predicts a transmembrane localization. Myeov was mapped to chromosome 11q13 and localized by DNA fiber fluorescence in situ hybridization (FISH) 360-kilobase (kb) centromeric of cyclin D1. In 3 of 7 multiple myeloma (MM) cell lines with a t(11;14)(q13;q32) and cyclin-D1 overexpression, Northern blot analysis revealed overexpression of myeov as well. In all 7 cell lines, the translocation breakpoint was mapped within the 360-kb region between myeov and cyclin D1. DNA fiber FISH with a contig of probes covering the constant region of the immunoglobulin heavy chain (IgH) revealed that exclusively in the 3 myeov-overexpressing cell lines (KMS-12, KMS-21, and XG-5), either the 5' E(mu) enhancer or the most telomeric 3' Ealpha enhancer was juxtaposed to myeov. Although cyclin D1 overexpression represents a characteristic feature of all MM cell lines with t(11;14), our results demonstrate aberrant expression of a second putative oncogene in a subset of these cases, due to juxtaposition to IgH enhancers. The clinical relevance of this dual activation remains to be elucidated. (Blood. 2000;95:2691-2698)
Janssen
J W
JW
Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany. hans_janssen@med.uni-heidelberg.de
Vaandrager
J W
JW
Heuser
T
T
Jauch
A
A
Kluin
P M
PM
Geelen
E
E
Bergsagel
P L
PL
Kuehl
W M
WM
Drexler
H G
HG
Otsuki
T
T
Bartram
C R
CR
Schuuring
E
E
D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D019938:Cyclin D1 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D019938:Cyclin D1