Genomic profile analysis of diffuse-type gastric cancers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-04

AUTHORS

Yeon-Su Lee, Yun Sung Cho, Geon Kook Lee, Sunghoon Lee, Young-Woo Kim, Sungwoong Jho, Hak-Min Kim, Seung-Hyun Hong, Jung-Ah Hwang, Sook-young Kim, Dongwan Hong, Il Ju Choi, Byung Chul Kim, Byoung-Chul Kim, Chul Hong Kim, Hansol Choi, Youngju Kim, Kyung Wook Kim, Gu Kong, Hyung Lae Kim, Jong Bhak, Seung Hoon Lee, Jin Soo Lee

ABSTRACT

BACKGROUND: Stomach cancer is the third deadliest among all cancers worldwide. Although incidence of the intestinal-type gastric cancer has decreased, the incidence of diffuse-type is still increasing and its progression is notoriously aggressive. There is insufficient information on genome variations of diffuse-type gastric cancer because its cells are usually mixed with normal cells, and this low cellularity has made it difficult to analyze the genome. RESULTS: We analyze whole genomes and corresponding exomes of diffuse-type gastric cancer, using matched tumor and normal samples from 14 diffuse-type and five intestinal-type gastric cancer patients. Somatic variations found in the diffuse-type gastric cancer are compared to those of the intestinal-type and to previously reported variants. We determine the average exonic somatic mutation rate of the two types. We find associated candidate driver genes, and identify seven novel somatic mutations in CDH1, which is a well-known gastric cancer-associated gene. Three-dimensional structure analysis of the mutated E-cadherin protein suggests that these new somatic mutations could cause significant functional perturbations of critical calcium-binding sites in the EC1-2 junction. Chromosomal instability analysis shows that the MDM2 gene is amplified. After thorough structural analysis, a novel fusion gene TSC2-RNF216 is identified, which may simultaneously disrupt tumor-suppressive pathways and activate tumorigenesis. CONCLUSIONS: We report the genomic profile of diffuse-type gastric cancers including new somatic variations, a novel fusion gene, and amplification and deletion of certain chromosomal regions that contain oncogenes and tumor suppressors. More... »

PAGES

r55

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/gb-2014-15-4-r55

    DOI

    http://dx.doi.org/10.1186/gb-2014-15-4-r55

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1009779388

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24690483


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    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/gb-2014-15-4-r55'

    Turtle is a human-readable linked data format.

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    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/gb-2014-15-4-r55'


     

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