Correlation of TACC3, FGFR3, MMSET and p21 expression with the t(4;14)(p16.3;q32) in multiple myeloma.
The t(4;14)(p16;q32) translocation seen in c. 18% of newly diagnosed multiple myeloma (MM) cases, results in FGFR3 activation and creation of an IGH/MMSET fusion transcript. We have recently shown that FGFR3 is activated in only 75% of t(4;14)(+) cases, suggesting that alternative genes near the breakpoint may be involved in the transforming event. The gene, TACC3, located just 50 kb telomeric of FGFR3, with transforming capacity, therefore represented a candidate gene. Using a real-time quantitative polymerase chain reaction-based approach on a cohort of 54 patients, we found a statistically significant, twofold increase in TACC3 expression in t(4;14)(+) cases. TACC3, MMSET and p21 values were positively correlated in all cases and, of particular interest, six patient samples [three t(4;14)(-), three t(4;14)(+)] samples showed a joint up-regulation of TACC3, MMSET and p21. Although a poor prognosis is linked with elevated MMSET expression, an extended follow-up period will be required to evaluate the significance of elevated TACC3 and p21 expression in this subgroup of MM.
Stewart
James Peter
JP
Haematology Research Group, Cancer Research Centre, Queen's University Belfast, Belfast BT9 7AB, UK.
Thompson
Alexander
A
Santra
Madhumita
M
Barlogie
Bart
B
Lappin
Terence R J
TR
Shaughnessy
John
J
D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14; D002894:Chromosomes, Human, Pair 4; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D005819:Genetic Markers; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
D002352:Carrier Proteins; D005819:Genetic Markers; D008869:Microtubule-Associated Proteins; D012097:Repressor Proteins; C120551:TACC3 protein, human; D011495:Histone-Lysine N-Methyltransferase; C419586:NSD2 protein, human; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)