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1. Supplementary Table 3 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Table 3 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
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2. Supplementary Table 9 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Table 9 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
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3. Supplementary Figure 1 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Figure 1 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
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4. Supplementary Table 8 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Table 8 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
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5. Supplementary Table 5 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Table 5 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
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6. Supplementary Table 4 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Table 4 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
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7. Supplementary Table 11 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Table 11 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
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8. Supplementary Table 2 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Table 2 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
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9. Supplementary Figure 3 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Figure 3 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
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10. Supplementary Table 10 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Table 10 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
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11. Supplementary Table 7 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Table 7 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
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12. Supplementary Table 1 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Table 1 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
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13. Supplementary Methods and Materials, Results, Legends for Tables 1-11 and Figures 1-3 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Methods and Materials, Results, Legends for Tables 1-11 and Figures 1-3 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
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14. Supplementary Table 6 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Table 6 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
Full Text
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15. Supplementary Figure 2 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Author

Patrick Tan, Bin Tean Teh, Steve Rozen, Liang Kee Goh, Kyle A. Furge, Heike Grabsch, P. Andrew Futreal, Yujing Liu, Siyu Lim, Jiong Tao, Anna Gan, Karl Dykema, Lian Dee Ler, Dachuan Huang, Shen Li Zhang, Willie Yu, Ioana Cutcutache, Choon Kiat Ong, and Zhi Jiang Zang

Abstract

Supplementary Figure 2 from Genetic and Structural Variation in the Gastric Cancer Kinome Revealed through Targeted Deep Sequencing

Published
2023
Full Text
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16. Genetic and structural variation in the gastric cancer kinome revealed through targeted deep sequencing

Author

Shen Li Zhang, Heike Grabsch, Bin Tean Teh, Patrick Tan, Anna Gan, Steve Rozen, Lian Dee Ler, Liang Kee Goh, Kyle A. Furge, Dachuan Huang, Ioana Cutcutache, Karl Dykema, Choon Kiat Ong, Zhi Jiang Zang, Yujing Liu, P. Andrew Futreal, Siyu Lim, Jiong Tao, and Willie Yu

Subjects
Nonsynonymous substitution, Genetics, Cancer Research, Sequence Homology, Amino Acid, Kinase, MAP Kinase Signaling System, Molecular Sequence Data, Gene Dosage, Genetic Variation, Biology, Deep sequencing, Article, Structural variation, Oncology, Stomach Neoplasms, Cell Line, Tumor, Genetic variation, Humans, Kinome, Amino Acid Sequence, Protein kinase A, Gene, Protein Kinases, Signal Transduction
Abstract

Genetic alterations in kinases have been linked to multiple human pathologies. To explore the landscape of kinase genetic variation in gastric cancer (GC), we used targeted, paired-end deep sequencing to analyze 532 protein and phosphoinositide kinases in 14 GC cell lines. We identified 10,604 single-nucleotide variants (SNV) in kinase exons including greater than 300 novel nonsynonymous SNVs. Family-wise analysis of the nonsynonymous SNVs revealed a significant enrichment in mitogen-activated protein kinase (MAPK)-related genes (P < 0.01), suggesting a preferential involvement of this kinase family in GC. A potential antioncogenic role for MAP2K4, a gene exhibiting recurrent alterations in 2 lines, was functionally supported by siRNA knockdown and overexpression studies in wild-type and MAP2K4 variant lines. The deep sequencing data also revealed novel, large-scale structural rearrangement events involving kinases including gene fusions involving CDK12 and the ERBB2 receptor tyrosine kinase in MKN7 cells. Integrating SNVs and copy number alterations, we identified Hs746T as a cell line exhibiting both splice-site mutations and genomic amplification of MET, resulting in MET protein overexpression. When applied to primary GCs, we identified somatic mutations in 8 kinases, 4 of which were recurrently altered in both primary tumors and cell lines (MAP3K6, STK31, FER, and CDKL5). These results demonstrate that how targeted deep sequencing approaches can deliver unprecedented multilevel characterization of a medically and pharmacologically relevant gene family. The catalog of kinome genetic variants assembled here may broaden our knowledge on kinases and provide useful information on genetic alterations in GC. Cancer Res; 71(1); 29–39. ©2011 AACR.

Published
2010

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