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.
Bibliographical noteFunding Information:
This project was funded by Department of Biotechnology (DBT), Govt. of India through the RNAi task force research grant BT/PR12893/AGR/36/628/2009 to Kumaresan Ganesan, Madurai Kamaraj University. NET-UGC fellowship support to Sembulingam Tamilzhalagan and DST-INSPIRE fellowship to Muthulakshmi Muthuswami are acknowledged. Instrumentation supports of UGC-CEGS, DBT-IPLS, UGC-NRCBS, UGC-CAS, and DST-PURSE programme supported central facilities of SBS, MKU are acknowledged. Our sincere thanks to Dr. Suresh Kumar Rayala, IIT Madras for his support with Akt, MAPK/ERK1/2 antibodies. Authors thank Ms. M. Niraimathi and Dr. A. Mahesh for technical support at MKU-HCS and MKU-FACS facility. We thank the TCGA research network for the accessibility of data.
© 2015 Elsevier Inc.
All Science Journal Classification (ASJC) codes
- Cell Biology