Computational analysis and experimental validation of tumor-associated alternative RNA splicing in human cancer.
A genome-wide computational screen was performed to identify tumor-associated alternative RNA splicing isoforms. A BLAST algorithm was used to compare 11,014 genes from RefSeq with 3,471,822 human expressed sequence tag sequences. The screen identified 26,258 alternative splicing isoforms of which 845 were significantly associated with human cancer, and 54 were specifically associated with liver cancer. Furthermore, canonical GT-AG splice junctions were used significantly less frequently in the alternative splicing isoforms in tumors. Reverse transcription-PCR experiments confirmed association of the alternative splicing isoforms with tumors. These results suggest that alternative splicing may have potential as a diagnostic marker for cancer.
Wang
Zhining
Z
Laboratory of Population Genetics, National Cancer Institute, National Institutes of Health, Gaithersburg, Maryland 20877,USA.
Lo
H Shuen
HS
Yang
Howard
H
Gere
Sheryl
S
Hu
Ying
Y
Buetow
Kenneth H
KH
Lee
Maxwell P
MP
D000465:Algorithms; D017398:Alternative Splicing; D019295:Computational Biology / Q000379:methods; D030561:Databases, Nucleic Acid; D020224:Expressed Sequence Tags; D005819:Genetic Markers / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005819:Genetic Markers