Dataset Information

Comprehensive genome- and transcriptome-wide analyses of mutations associated with microsatellite instability in Korean gastric cancers.

ABSTRACT: Microsatellite instability (MSI) is a critical mechanism that drives genetic aberrations in cancer. To identify the entire MS mutation, we performed the first comprehensive genome- and transcriptome-wide analyses of mutations associated with MSI in Korean gastric cancer cell lines and primary tissues. We identified 18,377 MS mutations of five or more repeat nucleotides in coding sequences and untranslated regions of genes, and discovered 139 individual genes whose expression was down-regulated in association with UTR MS mutation. In addition, we found that 90.5% of MS mutations with deletions in gene regions occurred in UTRs. This analysis emphasizes the genetic diversity of MSI-H gastric tumors and provides clues to the mechanistic basis of instability in microsatellite unstable gastric cancers.

SUBMITTER: Yoon K

PROVIDER: S-EPMC3698504 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Publications

Comprehensive genome- and transcriptome-wide analyses of mutations associated with microsatellite instability in Korean gastric cancers.

Yoon Kwiyeom K Lee Sunghoon S Han Tae-Su TS Moon So Yeon SY Yun Sun Mi SM Kong Seong-Ho SH Jho Sungwoong S Choe Jinny J Yu Jieun J Lee Hyuk-Joon HJ Park Ji Hyun JH Kim Hak-Min HM Lee So Yeun SY Park Jongsun J Kim Woo-Ho WH Bhak Jong J Yang Han-Kwang HK Kim Seong-Jin SJ

Genome research 20130604 7

Microsatellite instability (MSI) is a critical mechanism that drives genetic aberrations in cancer. To identify the entire MS mutation, we performed the first comprehensive genome- and transcriptome-wide analyses of mutations associated with MSI in Korean gastric cancer cell lines and primary tissues. We identified 18,377 MS mutations of five or more repeat nucleotides in coding sequences and untranslated regions of genes, and discovered 139 individual genes whose expression was down-regulated i ...[more]

PMID: 23737375

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Project description:Colorectal cancer is the second leading cause of cancer death worldwide, and the incidence of this disease is expected to increase as global socioeconomic changes occur. Immune checkpoint inhibition therapy is effective in treating a minority of colorectal cancer tumors; however, microsatellite stable tumors do not respond well to this treatment. Emerging cancer immunotherapeutic strategies aim to activate a cytotoxic T cell response against tumor-specific antigens, presented exclusively at the cell surface of cancer cells. These antigens are rare and are most effectively identified with a mass spectrometry-based approach, which allows the direct sampling and sequencing of these peptides. While the few tumor-specific antigens identified to date are derived from coding regions of the genome, recent findings indicate that a large proportion of tumor-specific antigens originate from allegedly noncoding regions. Here, we employed a novel proteogenomic approach to identify tumor antigens in a collection of colorectal cancer-derived cell lines and biopsy samples consisting of matched tumor and normal adjacent tissue. The generation of personalized cancer databases paired with mass spectrometry analyses permitted the identification of more than 30 000 unique MHC I-associated peptides. We identified 19 tumor-specific antigens in both microsatellite stable and unstable tumors, over two-thirds of which were derived from non-coding regions. Many of these peptides were derived from source genes known to be involved in colorectal cancer progression, suggesting that antigens from these genes could have therapeutic potential in a wide range of tumors. These findings could benefit the development of T cell-based vaccines, in which T cells are primed against these antigens to target and eradicate tumors. Such a vaccine could be used in tandem with existing immune checkpoint inhibition therapies, to bridge the gap in treatment efficacy across subtypes of colorectal cancer with varying prognoses. Data are available via ProteomeXchange with identifier PXD028309.

Dataset Information

Comprehensive genome- and transcriptome-wide analyses of mutations associated with microsatellite instability in Korean gastric cancers.

Publications

Comprehensive genome- and transcriptome-wide analyses of mutations associated with microsatellite instability in Korean gastric cancers.

Similar Datasets

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