PMID- 12368157
OWN - NLM
STAT- MEDLINE
DCOM- 20030113
LR  - 20120605
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 87
IP  - 10
DP  - 2002 Oct
TI  - Novel mutation and RNA splice variant of fibroblast growth factor receptor 3 in 
      multiple myeloma patients at diagnosis.
PG  - 1036-40
AB  - BACKGROUND AND OBJECTIVES: The karyotypically silent t(4;14)(p16.3;q32) 
      translocation can be found in approximately 15-20% of multiple myeloma (MM) 
      patients and results in the ectopic expression of fibroblast growth factor 
      receptor 3 (FGFR3) from der4. Point mutations in specific FGFR3 domains can be 
      found in the translocated allele, and have been recently proven to be oncogenic. 
      These mutations produce a constitutively activated receptor, which shows 
      dimerization and autophosphorylation even in the absence of ligand. We 
      investigated the presence of FGFR3 expression and activating mutations in a 
      series of newly diagnosed MM patients. DESIGN AND METHODS: We validated a new 
      sensitive and specific Taqman real-time reverse-transcription 
      polymerase-chain-reaction (RT-PCR) set up to evaluate FGFR3 mRNA expression, and 
      applied it to 78 newly diagnosed patients; in positive cases, FGFR3 mRNA 
      transcripts were sequenced. Fluorescence in situ hybridization (FISH) was done in 
      32 cases with sufficient material. RESULTS: Real-time RT-PCR revealed FGFR3 mRNA 
      expression in 10/78 (13%) patients. In two cases, sequence analysis revealed 
      novel FGFR3 mutations. In a patient with FISH evidence of the t(4;14), a CGC to 
      TGC transition was detected in codon 248. In a patient without the t(4;14), three 
      additional, abnormal-sized transcripts were detected, corresponding to truncated 
      transcripts originating from cryptic splice donor sites located within exon 7. 
      INTERPRETATION AND CONCLUSIONS: We describe a novel FGFR3 mutation (with a 
      demonstrated deregulatory mechanism), as well as a case of alternative splicing 
      in the absence of t(4;14), detected in newly diagnosed MM patients overexpressing 
      FGFR3. This implies that FGFR3 mutation can occur at an early stage of 
      myelomagenesis and even in the absence of the t(4;14).
FAU - Soverini, Simona
AU  - Soverini S
AD  - Institute of Hematology and Medical Oncology Seragnoli , University of Bologna, 
      Italy.
FAU - Terragna, Carolina
AU  - Terragna C
FAU - Testoni, Nicoletta
AU  - Testoni N
FAU - Ruggeri, Deborah
AU  - Ruggeri D
FAU - Tosi, Patrizia
AU  - Tosi P
FAU - Zamagni, Elena
AU  - Zamagni E
FAU - Cellini, Claudia
AU  - Cellini C
FAU - Cavo, Michele
AU  - Cavo M
FAU - Baccarani, Michele
AU  - Baccarani M
FAU - Tura, Sante
AU  - Tura S
FAU - Martinelli, Giovanni
AU  - Martinelli G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Fibroblast Growth Factor)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.10.1 (FGFR3 protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 3)
SB  - IM
MH  - *Alternative Splicing
MH  - Amino Acid Sequence
MH  - DNA Mutational Analysis
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - Multiple Myeloma/diagnosis/*genetics/metabolism
MH  - *Mutation
MH  - *Protein-Tyrosine Kinases
MH  - RNA/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptor, Fibroblast Growth Factor, Type 3
MH  - Receptors, Fibroblast Growth Factor/*genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Homology, Amino Acid
EDAT- 2002/10/09 04:00
MHDA- 2003/01/14 04:00
CRDT- 2002/10/09 04:00
PHST- 2002/10/09 04:00 [pubmed]
PHST- 2003/01/14 04:00 [medline]
PHST- 2002/10/09 04:00 [entrez]
PST - ppublish
SO  - Haematologica. 2002 Oct;87(10):1036-40.