Audrey S M Teo

Publications (3)24.33 Total impact

• Article: Whole-genome reconstruction and mutational signatures in gastric cancer.

  Niranjan Nagarajan, Denis Bertrand, Axel M Hillmer, Zhi Jiang Zang, Fei Yao, Pierre-Etienne Jacques, Audrey S M Teo, Ioanna Cutcutache, Zhenshui Zhang, Wah Heng Lee, [......], Jimmy B Y So, Guillaume Bourque, Richie Soong, Wing-Kin Sung, Bin Tean Teh, Steven Rozen, Xiaoan Ruan, Khay Guan Yeoh, Patrick B O Tan, Yijun Ruan
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  ABSTRACT: 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-PET 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 tumours 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.
  Genome biology 12/2012; 13(12):R115. · 6.63 Impact Factor
• Article: Long Span DNA Paired-End-Tag (DNA-PET) Sequencing Strategy for the Interrogation of Genomic Structural Mutations and Fusion-Point-Guided Reconstruction of Amplicons.

  Fei Yao, Pramila N Ariyaratne, Axel M Hillmer, Wah Heng Lee, Guoliang Li, Audrey S M Teo, Xing Yi Woo, Zhenshui Zhang, Jieqi P Chen, Wan Ting Poh, [......], Niranjan Nagarajan, Hervé Thoreau, Atif Shahab, Xiaoan Ruan, Valère Cacheux-Rataboul, Chia-Lin Wei, Guillaume Bourque, Wing-Kin Sung, Edison T Liu, Yijun Ruan
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  ABSTRACT: Structural variations (SVs) contribute significantly to the variability of the human genome and extensive genomic rearrangements are a hallmark of cancer. While genomic DNA paired-end-tag (DNA-PET) sequencing is an attractive approach to identify genomic SVs, the current application of PET sequencing with short insert size DNA can be insufficient for the comprehensive mapping of SVs in low complexity and repeat-rich genomic regions. We employed a recently developed procedure to generate PET sequencing data using large DNA inserts of 10-20 kb and compared their characteristics with short insert (1 kb) libraries for their ability to identify SVs. Our results suggest that although short insert libraries bear an advantage in identifying small deletions, they do not provide significantly better breakpoint resolution. In contrast, large inserts are superior to short inserts in providing higher physical genome coverage for the same sequencing cost and achieve greater sensitivity, in practice, for the identification of several classes of SVs, such as copy number neutral and complex events. Furthermore, our results confirm that large insert libraries allow for the identification of SVs within repetitive sequences, which cannot be spanned by short inserts. This provides a key advantage in studying rearrangements in cancer, and we show how it can be used in a fusion-point-guided-concatenation algorithm to study focally amplified regions in cancer.
  PLoS ONE 01/2012; 7(9):e46152. · 4.09 Impact Factor
• Article: Comprehensive long-span paired-end-tag mapping reveals characteristic patterns of structural variations in epithelial cancer genomes.

  Axel M Hillmer, Fei Yao, Koichiro Inaki, Wah Heng Lee, Pramila N Ariyaratne, Audrey S M Teo, Xing Yi Woo, Zhenshui Zhang, Hao Zhao, Leena Ukil, [......], Xiaoan Ruan, Jonas Bergh, Per Hall, Valère Cacheux-Rataboul, Chia-Lin Wei, Khay Guan Yeoh, Wing-Kin Sung, Guillaume Bourque, Edison T Liu, Yijun Ruan
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  ABSTRACT: Somatic genome rearrangements are thought to play important roles in cancer development. We optimized a long-span paired-end-tag (PET) sequencing approach using 10-Kb genomic DNA inserts to study human genome structural variations (SVs). The use of a 10-Kb insert size allows the identification of breakpoints within repetitive or homology-containing regions of a few kilobases in size and results in a higher physical coverage compared with small insert libraries with the same sequencing effort. We have applied this approach to comprehensively characterize the SVs of 15 cancer and two noncancer genomes and used a filtering approach to strongly enrich for somatic SVs in the cancer genomes. Our analyses revealed that most inversions, deletions, and insertions are germ-line SVs, whereas tandem duplications, unpaired inversions, interchromosomal translocations, and complex rearrangements are over-represented among somatic rearrangements in cancer genomes. We demonstrate that the quantitative and connective nature of DNA-PET data is precise in delineating the genealogy of complex rearrangement events, we observe signatures that are compatible with breakage-fusion-bridge cycles, and we discover that large duplications are among the initial rearrangements that trigger genome instability for extensive amplification in epithelial cancers.
  Genome Research 04/2011; 21(5):665-75. · 13.61 Impact Factor