Novel transcripts of fibroblast growth factor receptor 3 reveal aberrant splicing and activation of cryptic splice sequences in colorectal cancer.
A nested reverse transcription-PCR analysis of FGFR3 from human colorectal carcinomas revealed novel mutant transcripts caused by aberrant splicing and activation of cryptic splice sequences. Two aberrantly spliced transcripts were detected with high frequency in 50% of 36 primary tumors and in 60% of 10 human colorectal cancer cell lines. Most transcripts used normal splice sites but skipped or included exons 8 and 9. Two mutant transcripts arose from cryptic splice donor sites in exon 7 that spliced to exon 10. The predicted translation products would exhibit frameshifts and a premature termination codon in exon 10. We propose that dysregulation of mRNA splicing frequently generates an aberrant FGFR3 transcript that may confer a selectable advantage on clones of cells in colorectal tumorigenesis.
Jang
J H
JH
Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Korea.
Shin
K H
KH
Park
Y J
YJ
Lee
R J
RJ
McKeehan
W L
WL
Park
J G
JG
D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D018389:Codon, Nonsense; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005091:Exons / Q000235:genetics; D016368:Frameshift Mutation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D010443:Peptide Chain Termination, Translational; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D018389:Codon, Nonsense; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3