Corpas M.,The Genome Analysis Center |
Glusman G.,Institute for Systems Biology |
Cariaso M.,River Road Bio LLC |
Jimenez R.,European Bioinformatics Institute |
And 4 more authors.
F1000Research | Year: 2012
Direct-to-consumer (DTC) genetic testing is a recent commercial endeavor that allows the general public to access personal genomic data. The growing availability of personal genomic data has in turn stimulated the development of non-commercial tools for DTC data analysis. Despite this new wealth of public resources, no systematic research has been carried out to assess these tools for interpretation of DTC data. Here, we provide an initial analysis benchmark in the context of a whole family, using single nucleotide polymorphism (SNP) data. Five blood-related DTC SNP chip data tests were analyzed in conjunction with one whole exome sequence. We report findings related to genomic similarity between individuals, genetic risks and an overall assessment of data quality; thus providing an evaluation of the current potential of public domain analysis tools for personal genomics. We envisage that as the use of personal genome tests spreads to the general population, publicly available tools will have a more prominent role in the interpretation of genomic data in the context of health risks and ancestry. © 2012 Glusman G et al.
Lee B.,Korea University |
Lee B.,Sookmyung Womens University |
Yoon K.,Korea University |
Lee S.,Personal Genomics Institute |
And 11 more authors.
Genes Chromosomes and Cancer | Year: 2015
Homozygous deletion is a frequent mutational mechanism of silencing tumor suppressor genes in cancer. Therefore, homozygous deletions have been analyzed for identification of tumor suppressor genes that can be utilized as biomarkers or therapeutic targets for cancer treatment. In this study, to elucidate potential tumor suppressor genes involved in gastric cancer (GC), we analyzed the entire set of large homozygous deletions in six human GC cell lines through genome- and transcriptome-wide approaches. We identified 51 genes in homozygous deletion regions of chromosomes and confirmed the deletion frequency in tumor tissues of 219 GC patients from The Cancer Genome Atlas database. We evaluated the effect of homozygous deletions on the mRNA level and found significantly affected genes in chromosome bands 9p21, 3p22, 5p14, and 6q15. Among the genes in 9p21, we investigated the potential tumor suppressive effect of KLHL9. We demonstrated that ectopic expression of KLHL9 inhibited cell proliferation and tumor formation in KLHL9-deficient SNU-16 cell line. In addition, we observed that homozygous focal deletions generated truncated transcripts of TGFBR2, CTNNA1, and STXBP5. Ectopic expression of two kinds of TGFBR2-reverse GADL1 fusion genes suppressed TGF-β signaling, which may lead to the loss of sensitivity to TGF-β tumor suppressive activity. In conclusion, our findings suggest that novel tumor suppressor genes that are aberrantly expressed through homozygous deletions may play important roles in gastric tumorigenesis. © 2014 Wiley Periodicals, Inc.
Yun S.M.,CHA Medical University |
Yoon K.,CHA Medical University |
Lee S.,TheragenEtex Inc. |
Kim E.,CHA Medical University |
And 11 more authors.
Oncogene | Year: 2013
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.Oncogene advance online publication, 25 November 2013; doi:10.1038/onc.2013.472.
Choi S.-J.,Sungkyunkwan University |
Kim S.-H.,Sungkyunkwan University |
Kang H.Y.,TheragenEtex Inc. |
Lee J.,Sungkyunkwan University |
And 11 more authors.
Biochemical and Biophysical Research Communications | Year: 2011
We determined the somatic mutations in the mitochondrial genomes of 70 lung cancer patients by pair-wise comparative analyses of the normal- and tumor-genome sequences acquired using Affymetrix Mitochondrial Resequencing Array 2.0. The overall mutation rates in lung cancers were Approximately 100 fold higher than those in normal cells, with significant statistical correlation with smoking (p = 0.00088). Total of 532 somatic mutations were evenly distributed in 499 positions with very low overall frequency (1.07/bp), but the non-synonymous mutations causing amino acid substitution occurred more frequently (1.83/bp), particularly at two positions, 8701 and 10398 (10.5/bp) that code for ATPase6 and NADH dehydrogenase 3, respectively. Despite the randomness or even distribution of the mutations, these two mutations occurred together in 86% of the cases. The linkage between the two most frequent mutations suggests that they were selected together, possibly due to their cooperative role during cancer development. Indeed, the mutation at 10398 was shown by Canter, Pezzotti, and their colleagues in 2009, as a risk factor for breast cancer. In this study, we identified two potential biomarkers that might be functionally linked together during the development of cancer. © 2011 Elsevier Inc.