title: Upregulated, 7q21-22 amplicon candidate gene SHFM1 confers oncogenic advantage by suppressing p53 function in gastric cancer.
abstract: Chromosomal aberrations are hallmarks of cancers and the locus of frequent genomic amplifications often harbors key cancer driver genes. Many genomic amplicons remain larger with hundreds of genes and the key drivers remain to be identified by an amplification-wide systematic analysis. The 7q21.12-q22.3 genomic amplification is frequent in gastric cancers which occur in ~10% of the patients and multiple cell lines. This 7q21.12-q22.3 amplicon has not yet been completely analyzed towards identifying the driver genes and their functional contribution in oncogenesis. The amplitude and prevalence indicate the important role conferred by this amplicon in gastric cancers. Among the 159 genes of this amplicon, 12 genes are found over-expressed in primary gastric tumors and cell lines. Many of the over-expressed genes show negative association with p53 transcriptional activity. RNAi based functional screening of the genes reveal, SHFM1 as key gastric cancer driver gene. SHFM1 confers cell cycle progression and resistance to p53 stabilizing drugs in gastric cancer cells. SHFM1 also activates Src, MAPK/ERK and PI3K/Akt signaling pathways. This is the first integrative genomic investigation of 7q21.12-q22.3 amplicon revealing the potential oncogenic candidacy of 12 genes. The oncogenic contribution of SHFM1, mediated by the p53 suppressive feature has been demonstrated in gastric cancer cells.
authors.affiliation: Cancer Genetics Laboratory, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, India.
authors.forename: Sembulingam
authors.initials: S
authors.lastname: Tamilzhalagan
authors.affiliation: Cancer Genetics Laboratory, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, India.
authors.forename: Muthulakshmi
authors.initials: M
authors.lastname: Muthuswami
authors.affiliation: Cancer Genetics Laboratory, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, India.
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Periasamy
authors.affiliation: Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore.
authors.forename: Ming Hui
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Yonsei Cancer Centre, Yonsei Cancer Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.affiliation: Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
authors.affiliation: Cancer Genetics Laboratory, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, India. Electronic address: kumar@oncocellomics.org.
authors.forename: Kumaresan
authors.initials: K
authors.lastname: Ganesan
mesh_terms: D002897:Chromosomes, Human, Pair 7; D059565:G2 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D015854:Up-Regulation; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D046988:Proteasome Endopeptidase Complex; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D019061:src-Family Kinases; C484606:SEM1 protein, human
keywords: 7q21.12–22.3; Gastric cancer; Genomic amplification; SHFM1; SNP array; p53 pathway