title: PPP1R1B-STARD3 chimeric fusion transcript in human gastric cancer promotes tumorigenesis through activation of PI3K/AKT signaling.
abstract: Fusion genes act as potent oncogenes, resulting from chromosomal rearrangements or abnormal transcription in many human cancers. Although multiple gastric cancer genomes have been sequenced, the driving recurrent gene fusions have not been well characterized. Here, we used paired-end transcriptome sequencing to identify novel gene fusions in 18 human gastric cancer cell lines and 18 pairs of primary human gastric cancer tissues and their adjacent normal tissues. Multiple samples revealed expression of PPP1R1B-STARD3 fusion transcript. The presence of PPP1R1B-STARD3 correlated with elevated levels of PPP1R1B mRNA. PPP1R1B-STARD3 fusion transcript was detected in 21.3% of primary human gastric cancers but not in adjacent matched normal gastric tissues. Based on reverse transcription PCR analysis of DNA, unlike other fusions described in gastric cancer, the PPP1R1B-STARD3 appears to be generated by RNA processing without chromosomal rearrangement. Overexpression of PPP1R1B-STARD3 in MKN-28 significantly increased cell proliferation and colony formation. This increased proliferation was mediated by activation of phosphatidylinositol-3-kinase (PI3K)/AKT signaling. Furthermore, expression of PPP1R1B-STARD3 fusion transcript enhanced the tumor growth of MKN-28 cells in athymic nude mice. These findings show that PPP1R1B-STARD3 fusion transcript has a key role in subsets of gastric cancers through the activation of PI3K/AKT signaling.
authors.affiliation: 1] CHA Cancer Institute, CHA University, Seoul, Korea [2] Department of Biomedical Science, College of Life Science, CHA University, 605 Yeoksam-dong, Gangnam-gu, Seoul, Korea.
authors.forename: S M
authors.initials: SM
authors.lastname: Yun
authors.affiliation: CHA Cancer Institute, CHA University, Seoul, Korea.
authors.forename: K
authors.initials: K
authors.lastname: Yoon
authors.affiliation: 1] Personal Genomics Institute, Genome Research Foundation, Suwon, Korea [2] TheragenEtex Bio Institute, TheragenEtex Inc., Suwon, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.affiliation: CHA Cancer Institute, CHA University, Seoul, Korea.
authors.forename: E
authors.initials: E
authors.lastname: Kim
authors.affiliation: 1] Cancer Research Institute, Seoul National University, Seoul, Korea [2] Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Kong
authors.affiliation: CHA Cancer Institute, CHA University, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Choe
authors.affiliation: CHA Cancer Institute, CHA University, Seoul, Korea.
authors.forename: J M
authors.initials: JM
authors.lastname: Kang
authors.affiliation: Cancer Research Institute, Seoul National University, Seoul, Korea.
authors.forename: T-S
authors.initials: TS
authors.lastname: Han
authors.affiliation: CHA Cancer Institute, CHA University, Seoul, Korea.
authors.forename: P
authors.initials: P
authors.lastname: Kim
authors.affiliation: CHA Cancer Institute, CHA University, Seoul, Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Personal Genomics Institute, Genome Research Foundation, Suwon, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Jho
authors.affiliation: CHA Cancer Institute, CHA University, Seoul, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Yoo
authors.affiliation: 1] Personal Genomics Institute, Genome Research Foundation, Suwon, Korea [2] TheragenEtex Bio Institute, TheragenEtex Inc., Suwon, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Bhak
authors.affiliation: 1] Cancer Research Institute, Seoul National University, Seoul, Korea [2] Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: H-K
authors.initials: HK
authors.lastname: Yang
authors.affiliation: 1] CHA Cancer Institute, CHA University, Seoul, Korea [2] Department of Biomedical Science, College of Life Science, CHA University, 605 Yeoksam-dong, Gangnam-gu, Seoul, Korea.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008819:Mice, Nude; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D002867:Chromones; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009025:Morpholines; D015514:Oncogene Proteins, Fusion; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C497928:PPP1R1B protein, human; C000594765:PPP1R1B-STARD3 oncogene fusion protein, human; C105684:STARD3 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one