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Whole-genome reconstruction and mutational signatures in gastric cancer.

Publication ,  Journal Article
Nagarajan, N; Bertrand, D; Hillmer, AM; Zang, ZJ; Yao, F; Jacques, P-É; Teo, ASM; Cutcutache, I; Zhang, Z; Lee, WH; Sia, YY; Gao, S; Ho, A ...
Published in: Genome Biol
December 13, 2012

BACKGROUND: Gastric cancer is the second highest cause of global cancer mortality. To explore the complete repertoire of somatic alterations in gastric cancer, we combined massively parallel short read and DNA paired-end tag sequencing to present the first whole-genome analysis of two gastric adenocarcinomas, one with chromosomal instability and the other with microsatellite instability. RESULTS: Integrative analysis and de novo assemblies revealed the architecture of a wild-type KRAS amplification, a common driver event in gastric cancer. We discovered three distinct mutational signatures in gastric cancer--against a genome-wide backdrop of oxidative and microsatellite instability-related mutational signatures, we identified the first exome-specific mutational signature. Further characterization of the impact of these signatures by combining sequencing data from 40 complete gastric cancer exomes and targeted screening of an additional 94 independent gastric tumors uncovered ACVR2A, RPL22 and LMAN1 as recurrently mutated genes in microsatellite instability-positive gastric cancer and PAPPA as a recurrently mutated gene in TP53 wild-type gastric cancer. CONCLUSIONS: These results highlight how whole-genome cancer sequencing can uncover information relevant to tissue-specific carcinogenesis that would otherwise be missed from exome-sequencing data.

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Published In

Genome Biol

DOI

EISSN

1474-760X

Publication Date

December 13, 2012

Volume

13

Issue

12

Start / End Page

R115

Location

England

Related Subject Headings

  • Stomach Neoplasms
  • Reactive Oxygen Species
  • Mutation
  • Microsatellite Instability
  • High-Throughput Nucleotide Sequencing
  • Genomics
  • Exome
  • Deamination
  • DNA Mutational Analysis
  • Chromosomal Instability
 

Citation

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Nagarajan, N., Bertrand, D., Hillmer, A. M., Zang, Z. J., Yao, F., Jacques, P.-É., … Ruan, Y. (2012). Whole-genome reconstruction and mutational signatures in gastric cancer. Genome Biol, 13(12), R115. https://doi.org/10.1186/gb-2012-13-12-r115
Nagarajan, Niranjan, Denis Bertrand, Axel M. Hillmer, Zhi Jiang Zang, Fei Yao, Pierre-Étienne Jacques, Audrey S. M. Teo, et al. “Whole-genome reconstruction and mutational signatures in gastric cancer.Genome Biol 13, no. 12 (December 13, 2012): R115. https://doi.org/10.1186/gb-2012-13-12-r115.
Nagarajan N, Bertrand D, Hillmer AM, Zang ZJ, Yao F, Jacques P-É, et al. Whole-genome reconstruction and mutational signatures in gastric cancer. Genome Biol. 2012 Dec 13;13(12):R115.
Nagarajan, Niranjan, et al. “Whole-genome reconstruction and mutational signatures in gastric cancer.Genome Biol, vol. 13, no. 12, Dec. 2012, p. R115. Pubmed, doi:10.1186/gb-2012-13-12-r115.
Nagarajan N, Bertrand D, Hillmer AM, Zang ZJ, Yao F, Jacques P-É, Teo ASM, Cutcutache I, Zhang Z, Lee WH, Sia YY, Gao S, Ariyaratne PN, Ho A, Woo XY, Veeravali L, Ong CK, Deng N, Desai KV, Khor CC, Hibberd ML, Shahab A, Rao J, Wu M, Teh M, Zhu F, Chin SY, Pang B, So JBY, Bourque G, Soong R, Sung W-K, Tean Teh B, Rozen S, Ruan X, Yeoh KG, Tan PBO, Ruan Y. Whole-genome reconstruction and mutational signatures in gastric cancer. Genome Biol. 2012 Dec 13;13(12):R115.

Published In

Genome Biol

DOI

EISSN

1474-760X

Publication Date

December 13, 2012

Volume

13

Issue

12

Start / End Page

R115

Location

England

Related Subject Headings

  • Stomach Neoplasms
  • Reactive Oxygen Species
  • Mutation
  • Microsatellite Instability
  • High-Throughput Nucleotide Sequencing
  • Genomics
  • Exome
  • Deamination
  • DNA Mutational Analysis
  • Chromosomal Instability