Nat Genet  1997 Jul;16(3):260-4 

Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated
with increased expression and activating mutations of fibroblast growth factor
receptor 3.

Chesi M, Nardini E, Brents LA, Schrock E, Ried T, Kuehl WM, Bergsagel PL.

Genetics Department, National Cancer Institute, Bethesda, Maryland 20889-5105,
USA.

Dysregulation of oncogenes by translocation to the IgH locus (14q32) is a
seminal event in the pathogenesis of B-cell tumours. In multiple myeloma (MM),
translocations to the IgH locus have been reported at an incidence of 20-60%.
For most translocations, the partner chromosome is unknown (14q+); for the
others, a diverse array of chromosomal partners have been identified, with 11q13
(cyclin D1) the only chromosome that is frequently involved. Recently, we
developed a Southern-blot assay that detects translocation breakpoint fragments
in most MM tumours, including those with no translocation detected by
conventional karyotyping. In a continuing analysis of translocation in 21
myeloma cell lines and primary tumours, we show that the novel, karyotypically
silent translocation t(4;14)(p16.3;q32.3) is present in five lines and at least
three of ten primary tumours. The chromosome-4 breakpoints are clustered in a
70-kb region centromeric to the fibroblast growth factor receptor 3 gene
(FGFR3), the apparent dysregulated oncogene. Two lines and one primary tumour
with this translocation selectively express an FGFR3 allele containing
activating mutations identified previously in thanatophoric dwarfism. We propose
that after the t(4;14) translocation, somatic mutation during tumour progression
frequently generates in FGFR3 protein that is active in the absence of ligand.

PMID: 9207791 [PubMed - indexed for MEDLINE]