Juxtaposed genes in 7q21-22 amplicon contribute for two major gastric cancer sub-Types by mutual exclusive expression.
Genomic Copy Number Variations (CNV) and the associated gene signatures are useful for cancer prognosis, diagnosis, and targeted therapeutics. Earlier, 7q21-22 region was reported for frequent amplification in gastric cancer and potential candidate genes were identified. An analysis of the expression pattern of the 159 genes located in this amplicon revealed the consistent elevated expression of 21 genes in gastric tumors. These genes are closely arranged within the 20 Mb region, and they showed a bimodal expression pattern. SHFM1 and 14 other genes are expressed in intestinal type gastric tumors. COL1A2 and PCOLCE genes of this region are expressed in diffuse type gastric tumors. Similarly, genome-wide expression neighbors of SHFM1 and COL1A2 also showed mutually exclusive expression pattern, and stratify intestinal and diffuse type gastric tumors. The expression of COL1A2 gene-set is associated with poor prognosis, whereas the SHFM1 gene-set is associated with better prognosis among the gastric cancer patients. Despite being physical neighbors, the SHFM1 and COL1A2 genes express differentially in the two major clinical sub-types of gastric cancer in a mutually exclusive manner. The tight gene regulations operating between these juxtaposed genes deserve investigation to understand the molecular regulatory switch defining the determinants of the gastric cancer sub-types. © 2016 Wiley Periodicals, Inc.
Unit of Excellence in Cancer Genetics, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, India.
Sembulingam
S
Tamilzhalagan
Unit of Excellence in Cancer Genetics, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, India.
Muthulakshmi
M
Muthuswami
Unit of Excellence in Cancer Genetics, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, India.
Kumaresan
K
Ganesan
D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D024042:Collagen Type I / Q000235:genetics; D056915:DNA Copy Number Variations; D005753:Gastric Mucosa / Q000378:metabolism; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D016019:Survival Analysis
C000601279:COL1A2 protein, human; D024042:Collagen Type I; C484606:SEM1 protein, human; D046988:Proteasome Endopeptidase Complex
COL1A2; SHFM1; diffuse; genomic amplification; intestinal