Transcriptome analysis of human gastric cancer
Laboratory of Human Genomics, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon , 305-333, Korea. Mammalian Genome
(Impact Factor: 3.07).
01/2006; 16(12):942-54. DOI: 10.1007/s00335-005-0075-2
To elucidate the genetic events associated with gastric cancer, 124,704 cDNA clones were collected from 37 human gastric cDNA libraries, including 20 full-length enriched cDNA libraries of gastric cancer cell lines and tissues from Korean patients. An analysis of the collected ESTs revealed that 97,930 high-quality ESTs coalesced into 13,001 clusters, of which 11,135 clusters (85.6%) were annotated to known ESTs. The analysis of the full-length cDNAs also revealed that 4862 clusters (51.7%) contained at least one putative full-length cDNA clone with an initiation codon, with the average length of the 5' UTR of 140 bp. A large number appear to have a diverse transcription start site (TSS). An examination of the TSS of some genes, such as TEGT and GAPD, using 5' RACE revealed that the predicted TSSs are actually found in human gastric cancer cells and that several TSSs differ depending on the specific gastric cell line. Furthermore, of the human gastric ESTs, 766 genes (9.5%) were present as putative alternatively spliced variants. Confirmation of the predicted spliced isoforms using RT-PCR showed that the predicted isoforms exist in gastric cancer cells and some isoforms coexist in gastric cell lines. These results provide potentially useful information for elucidating the molecular mechanisms associated with gastric oncogenesis.
Available from: Luis G Carvajal Carmona
- "TOPBP1 (topoisomerase DNA II-binding protein 1) represents a very interesting candidate for CRC genetic susceptibility as it contains multiple BRCT domains, the C-terminal portion of the BRCA-1 gene, and it has a critical role in the control of DNA damage and replication checkpoint (Gong et al, 2010). On the other hand, CDV3 (carnitine deficiency-associated gene expressed in ventricle 3), also known as H41, seems to be involved in cell proliferation and altered in gastric cancer (Oh et al, 2005). It is noteworthy that the TOPBP1 and CDV3 genes lie next to each other in 3q22 and rs1444601 and rs13088006 are only 34 kb apart. "
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ABSTRACT: Colorectal cancer (CRC) is the second cause of cancer-related death in the Western world. Much of the CRC genetic risk remains unidentified and may be attributable to a large number of common, low-penetrance genetic variants. Genetic linkage studies in CRC families have reported additional association with regions 9q22-31, 3q21-24, 7q31, 11q, 14q and 22q. There are several plausible candidate genes for CRC susceptibility within the aforementioned linkage regions including PTCH1, XPA and TGFBR1 in 9q22-31, and EPHB1 and MRAS in 3q21-q24.
CRC cases and matched controls were from EPICOLON, a prospective, multicentre, nationwide Spanish initiative, composed of two independent phases. Phase 1 corresponded to 515 CRC cases and 515 controls, whereas phase 2 consisted of 901 CRC cases and 909 controls. Genotyping was performed for 172 single-nucleotide polymorphisms (SNPs) in 84 genes located within regions 9q22-31 and 3q21-q24.
None of the 172 SNPs analysed in our study could be formally associated with CRC risk. However, rs1444601 (TOPBP1) and rs13088006 (CDV3) in region 3q22 showed interesting results and may have an effect on CRC risk.
TOPBP1 and CDV3 genetic variants on region 3q22 may modulate CRC risk. Further validation and meta-analysis should be undertaken in larger CRC cohorts.
British Journal of Cancer 08/2011; 105(6):870-5. DOI:10.1038/bjc.2011.296 · 4.84 Impact Factor
Available from: David Waugh
- "Unlike KsgA, ErmC 0 from Bacillus subtilis (Bs-ErmC 0 ) can methylate a fragment of 23S RNA as small as 32 nucleotides (Schluckebier et al., 1999; Weisblum, 1995). KsgA orthologs from nonbacterial sources are represented by Dim1 from Saccharomyces cerevisiae (Sc-Dim1) (Lafontaine et al., 1995, 1998) and from human (Hs-Dim1) (Law et al., 1998; Oh et al., 2005), Pfc1 from Arabidopsis thaliana (Tokuhisa et al., 1998), and mitochondria mtTFB from human (Hs-mtTFB) (Cotney and Shadel, 2006; McCulloch et al., 2002; Seidel-Rogol et al., 2003). The mtTFB from yeast (Sc-mtTFB), however, has lost its MTase activity (Klootwijk et al., 1975). "
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ABSTRACT: Among methyltransferases, KsgA and the reaction it catalyzes are conserved throughout evolution. However, the specifics of substrate recognition by the enzyme remain unknown. Here we report structures of Aquifex aeolicus KsgA, in its ligand-free form, in complex with RNA, and in complex with both RNA and S-adenosylhomocysteine (SAH, reaction product of cofactor S-adenosylmethionine), revealing critical structural information on KsgA-RNA and KsgA-SAH interactions. Moreover, the structures show how conformational changes that occur upon RNA binding create the cofactor-binding site. There are nine conserved functional motifs (motifs I-VIII and X) in KsgA. Prior to RNA binding, motifs I and VIII are flexible, each exhibiting two distinct conformations. Upon RNA binding, the two motifs become stabilized in one of these conformations, which is compatible with the binding of SAH. Motif X, which is also stabilized upon RNA binding, is directly involved in the binding of SAH.
Structure 04/2009; 17(3):374-85. DOI:10.1016/j.str.2009.01.010 · 5.62 Impact Factor
Available from: Boris Lenhard
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ABSTRACT: We introduce the Gene Characterization Index, a bioinformatics method for scoring the extent to which a protein-encoding gene is functionally described. Inherently a reflection of human perception, the Gene Characterization Index is applied for assessing the characterization status of individual genes, thus serving the advancement of both genome annotation and applied genomics research by rapid and unbiased identification of groups of uncharacterized genes for diverse applications such as directed functional studies and delineation of novel drug targets.
The scoring procedure is based on a global survey of researchers, who assigned characterization scores from 1 (poor) to 10 (extensive) for a sample of genes based on major online resources. By evaluating the survey as training data, we developed a bioinformatics procedure to assign gene characterization scores to all genes in the human genome. We analyzed snapshots of functional genome annotation over a period of 6 years to assess temporal changes reflected by the increase of the average Gene Characterization Index. Applying the Gene Characterization Index to genes within pharmaceutically relevant classes, we confirmed known drug targets as high-scoring genes and revealed potentially interesting novel targets with low characterization indexes. Removing known drug targets and genes linked to sequence-related patent filings from the entirety of indexed genes, we identified sets of low-scoring genes particularly suited for further experimental investigation.
The Gene Characterization Index is intended to serve as a tool to the scientific community and granting agencies for focusing resources and efforts on unexplored areas of the genome. The Gene Characterization Index is available from http://cisreg.ca/gci/.
PLoS ONE 02/2008; 3(1):e1440. DOI:10.1371/journal.pone.0001440 · 3.23 Impact Factor
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