Genomic landscape and genetic heterogeneity in gastric adenocarcinoma revealed by whole-genome sequencing

Wong, Suei Nee; Kim, Kyoung‐Mee; Ting, Jason C.; Yu, Kun; Fu, Jake; Liu, Shawn; Cristescu, Rǎzvan; Nebozhyn, Michael; Gong, Lara; Yue, Yong; Wang, Jian; Chen, Ronghua; Loboda, Andrey; Hardwick, James S.; Liu, Xiaoqiao; Dai, Hongyue; Jin, Jiamin; Ye, Xiang S.; Kang, So Young; Gu, In; Park, Joon Oh; Sohn, Tae Sung; Reinhard, Christoph; Lee, Jeeyun; Kim, Sung Hoon; Aggarwal, Amit

doi:10.1038/ncomms6477

Cited by 168 publications

(169 citation statements)

References 38 publications

(47 reference statements)

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“…Furthermore, large-scale genomic studies discovered frequent mutations in SLIT/ROBO pathway genes in gastric cancer (26), pancreatic cancer (27), and small-cell lung cancer (28). These studies suggest that the SLIT/ROBO pathway is a master regulator for multiple oncogenic signaling pathways and a promising target for cancer therapy (8,9).…”

Section: Discussionmentioning

confidence: 96%

Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes

Kim

Baek

et al. 2016

International Journal of Oncology

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Abstract. SLIT has been suggested as a key regulator of cancer development and a promising therapeutic target for cancer treatment. Herein, we analyzed expression and methylation of SLIT1/SLIT2/SLIT3 in 11 gastric cancer cell lines, 96 paired gastric tumors and adjacent normal gastric tissues, and 250 gastric cancers provided by The Cancer Genome Atlas. Methylation of SLIT1/SLIT2/SLIT3 was found both in early gastric cancers, and in advanced gastric cancers. Even normal gastric tissue showed increased methylation of SLIT1 and SLIT3 that correlated with patient age. Furthermore, epigenetic inactivation of SLIT occurred in a gastric cancer subtype-dependent manner. SLIT2 and SLIT3 expression was reduced in Epstein-Barr virus-positive and microsatellite instability subtypes, but increased in the genomically stable subtype. Expression of miR-218 correlated negatively with methylation of SLIT2 or SLIT3. These findings suggest that a molecular subtype-specific therapeutic strategy is needed for targeting SLITs and miR-218 in treatment of gastric cancer.

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Section: Discussionmentioning

confidence: 96%

Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes

Kim

Baek

et al. 2016

International Journal of Oncology

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“…These data suggest potential therapeutic role for PI3K (3,4). In this study, 300 GC were profiled using gene expression, genome-wide copy number microarray and targeted sequencing, yielding four distinct molecular subtypes.…”

Section: Gastric Cancer (Gc)mentioning

confidence: 97%

“…( (3,4) supplemented the TCGA analysis (2) by introducing TP53 activity and EMT in the classification. The two studies had similarities and differences.…”

Section: Gastric Cancer (Gc)mentioning

confidence: 99%

Molecular landscape and sub-classification of gastrointestinal cancers: a review of literature

Fakhri¹,

Lim²

2017

J. Gastrointest. Oncol.

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Abstract:The historical approach of diagnosing cancer types based entirely on anatomic origin and histologic features, and the "one-size-fit-all" therapeutic approach, are inadequate in modern cancer treatment. From decades of research we now know that cancer is a highly heterogeneous disease driven by complex genetic or epigenetic alterations. The advent of various high throughput molecular tools has now enabled us to view and sub-classify each cancer type based on their distinct molecular features, in addition to histologic classification, with the promise of individualized treatment strategies tailored towards each specific subtype to improve patient outcomes. In this review, we have made an effort to systematically review the most up-to-date, leading literature in molecular analysis and/or subtyping of major gastrointestinal cancers. These include esophageal squamous cell carcinoma (ESCC), gastric cancer (GC) adenocarcinoma, pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), gallbladder cancer (GBC), and colorectal cancer (CRC). For each cancer type we summarized the global mutational landscape, subgroup classification based on genomics, epigenetics, gene expression and/or proteomic analysis, and their salient clinicopathological features. We have highlighted the actionable mutations or mutational pathways that could help guide targeted therapies in the future.

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“…Alternative GAC-classifications have been proposed, and since 2014 molecular classifications start being more widely adopted. Some articles suggested classifying GACs as Epstein-Barr virus positive tumors (EBV), lesions with microsatellite instability (MSI) and those presenting chromosomal instability (CIN) [18][19][20][21].…”

Section: Molecular Studies Of Gastric Adenocarcinomasmentioning

confidence: 99%

Genomics and epidemiology for gastric adenocarcinomas

2017

Appl Cancer Res

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Whereas the pathological aspects of Gastric Adenocarcinomas (GACs) have been well defined, the actual knowledge of its genesis and evolution remains to be translated to better diagnosis and to more effective therapeutics. As a consequence, the current treatment modalities are not yet able to modify the natural history of the disease, which still presents high mortality-rates worldwide. In this review we highlight the current status of relevant epidemiologic, therapeutic and genomics aspects of GACs and point to some of the current knowledge gaps that, if fully addressed, could contribute to a more effective treatment and better management of the patients that suffer from this often-lethal disease.

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Genomic landscape and genetic heterogeneity in gastric adenocarcinoma revealed by whole-genome sequencing

Cited by 168 publications

References 38 publications

Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes

Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes

Molecular landscape and sub-classification of gastrointestinal cancers: a review of literature

Genomics and epidemiology for gastric adenocarcinomas

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