title: Correlation of TACC3, FGFR3, MMSET and p21 expression with the t(4;14)(p16.3;q32) in multiple myeloma.
abstract: 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.
authors.affiliation: Haematology Research Group, Cancer Research Centre, Queen's University Belfast, Belfast BT9 7AB, UK.
authors.forename: James Peter
authors.initials: JP
authors.lastname: Stewart
authors.forename: Alexander
authors.initials: A
authors.lastname: Thompson
authors.forename: Madhumita
authors.initials: M
authors.lastname: Santra
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: Terence R J
authors.initials: TR
authors.lastname: Lappin
authors.forename: John
authors.initials: J
authors.lastname: Shaughnessy
mesh_terms: 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
chemical_list: 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)