Loss of Heterozygosity at the Calcium Regulation Gene Locus on Chromosome 10q in Human Pancreatic Cancer


Background: Loss of heterozygosity (LOH) on chromosomal regions is crucial in tumor progression andthis study aimed to identify genome-wide LOH in pancreatic cancer. Materials and
Methods: Single-nucleotidepolymorphism (SNP) profiling data GSE32682 of human pancreatic samples snap-frozen during surgerywere downloaded from Gene Expression Omnibus database. Genotype console software was used to performdata processing. Candidate genes with LOH were screened based on the genotype calls, SNP loci of LOH anddbSNP database. Gene annotation was performed to identify the functions of candidate genes using NCBI (theNational Center for Biotechnology Information) database, followed by Gene Ontology, INTERPRO, PFAM andSMART annotation and UCSC Genome Browser track to the unannotated genes using DAVID (the Databasefor Annotation, Visualization and Integration Discovery).
Results: The candidate genes with LOH identified inthis study were MCU, MICU1 and OIT3 on chromosome 10. MCU was found to encode a calcium transporterand MICU1 could encode an essential regulator of mitochondrial Ca2+ uptake. OIT3 possibly correlated withcalcium binding revealed by the annotation analyses and was regulated by a large number of transcription factorsincluding STAT, SOX9, CREB, NF-kB, PPARG and p53.
Conclusions: Global genomic analysis of SNPs identifiedMICU1, MCU and OIT3 with LOH on chromosome 10, implying involvement of these genes in progression ofpancreatic cancer.