title: Whole-genome reconstruction and mutational signatures in gastric cancer.
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 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.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Nagarajan
authors.forename: Denis
authors.initials: D
authors.lastname: Bertrand
authors.forename: Axel M
authors.initials: AM
authors.lastname: Hillmer
authors.forename: Zhi Jiang
authors.initials: ZJ
authors.lastname: Zang
authors.forename: Fei
authors.initials: F
authors.lastname: Yao
authors.forename: Pierre-Étienne
authors.initials: PÉ
authors.lastname: Jacques
authors.forename: Audrey S M
authors.initials: AS
authors.lastname: Teo
authors.forename: Ioana
authors.initials: I
authors.lastname: Cutcutache
authors.forename: Zhenshui
authors.initials: Z
authors.lastname: Zhang
authors.forename: Wah Heng
authors.initials: WH
authors.lastname: Lee
authors.forename: Yee Yen
authors.initials: YY
authors.lastname: Sia
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.forename: Pramila N
authors.initials: PN
authors.lastname: Ariyaratne
authors.forename: Andrea
authors.initials: A
authors.lastname: Ho
authors.forename: Xing Yi
authors.initials: XY
authors.lastname: Woo
authors.forename: Lavanya
authors.initials: L
authors.lastname: Veeravali
authors.forename: Choon Kiat
authors.initials: CK
authors.lastname: Ong
authors.forename: Niantao
authors.initials: N
authors.lastname: Deng
authors.forename: Kartiki V
authors.initials: KV
authors.lastname: Desai
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
authors.forename: Atif
authors.initials: A
authors.lastname: Shahab
authors.forename: Jaideepraj
authors.initials: J
authors.lastname: Rao
authors.forename: Mengchu
authors.initials: M
authors.lastname: Wu
authors.forename: Ming
authors.initials: M
authors.lastname: Teh
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Sze Yung
authors.initials: SY
authors.lastname: Chin
authors.forename: Brendan
authors.initials: B
authors.lastname: Pang
authors.forename: Jimmy B Y
authors.initials: JB
authors.lastname: So
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bourque
authors.forename: Richie
authors.initials: R
authors.lastname: Soong
authors.forename: Wing-Kin
authors.initials: WK
authors.lastname: Sung
authors.forename: Bin
authors.initials: B
authors.lastname: Tean Teh
authors.forename: Steven
authors.initials: S
authors.lastname: Rozen
authors.forename: Xiaoan
authors.initials: X
authors.lastname: Ruan
authors.forename: Khay Guan
authors.initials: KG
authors.lastname: Yeoh
authors.forename: Patrick B O
authors.initials: PB
authors.lastname: Tan
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D043171:Chromosomal Instability; D004252:DNA Mutational Analysis / Q000379:methods*; D003641:Deamination; D059472:Exome; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D053842:Microsatellite Instability; D009154:Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D017382:Reactive Oxygen Species