Whole genome and transcriptome sequencing of matched primary and peritoneal metastatic gastric carcinoma

Zhang, Jie; Huang, Jiawen; Chen, Yixuan; Yuan, Fei; Zhang, H.; Yan, Feng; Wang, M. J.; Wang, G.; Su, Mingwan; Lu, Guankun; Huang, Yi; Dai, Hong Jie; Ji, Jun; Zhang, J. N.; Jiang, Yannan; Chen, S. J.; Zhu, Zhenggang; Yu, Yingyan

doi:10.1038/srep13750

Cited by 80 publications

(73 citation statements)

References 28 publications

(28 reference statements)

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“…Only one study mentioned that IQUB expression was increased in gastric cancer by transcriptome sequencing 5. In our study, we noticed that the expression of IQUB in breast cancer tissues was not only significantly increased, but also positively correlated with the pathological differentiation of breast cancer, suggesting that IQUB may have a bearing on the malignant progression and prognosis of breast cancer.…”

Section: Discussionsupporting

confidence: 52%

“…However, there were few studies exploring the role of IQUB in human diseases. Only one tumor‐related study referred to IQUB which found that IQUB was upregulated in gastric cancer tissues by transcriptome sequencing,5 but the mechanism was not clear. Combined with our transcriptome sequencing in breast cancer, we speculated that IQUB may act an important role in the development of tumor.…”

Section: Introductionmentioning

confidence: 99%

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Upregulated IQUB promotes cell proliferation and migration via activating Akt/GSK3β/β‐catenin signaling pathway in breast cancer

Zhang

et al. 2018

Cancer Medicine

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Breast cancer was the highest incidence of tumor in women, which seriously threaten women's health. Our previous study found that the expression of IQUB (IQ motif and ubiquitin domain containing) was significantly increased in the development of breast cancer by transcriptome sequencing. However, there were no studies on the mechanism of IQUB in tumorigenesis. Further study showed that IQUB expression was significantly increased in breast cancer, which had a significantly positive correlation with pathological differentiation of breast cancer by tissue microarray analysis. Furthermore, we also discovered that IQUB overexpression could obviously promote the proliferation and migration of MCF‐7 cells and increase the proportion of MCF‐7 cells in S and G2/M phase in vitro study, while knockdown of IQUB caused inhibition of cell proliferation and migration in MDA‐MB‐231 cells and increased the proportion of MDA‐MB‐231 cells in G1 phase. Furthermore, IQUB overexpression or knockdown combined with treatment of Licl or MG‐132 showed that IQUB activated Akt to promote GSK3β phosphorylation, which in turn activated Wnt/β‐catenin signaling pathway in breast cancer cells. Taken together, these results indicated that upregulated IQUB promoted breast cancer cell proliferation and migration via activating Akt/GSK3β/β‐catenin signaling pathway, which played an important part in the tumorigenesis and development of breast cancer.

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Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Upregulated IQUB promotes cell proliferation and migration via activating Akt/GSK3β/β‐catenin signaling pathway in breast cancer

Zhang

et al. 2018

Cancer Medicine

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“…Catumaxomab, an anti-EpCAM monoclonal antibody, coupled with intraperitoneally administered paclitaxel are recommended to effectively relieve gastric cancer-derived peritoneal metastasis [25]. Zhang et al recently identified 27 somatic mutated genes and infusion of GPX4 and MPND in the19q13.3-13.4 region by whole-genome and -transcriptome sequencing of one patient [4]. The different mutation events in the present study may be attributable to the different pathological characteristics of the selected specimen.…”

Section: Discussionmentioning

confidence: 83%

“…Although a steady decline in cancer incidence and mortality have been observed in recent years, an estimated 951,600 new gastric cancer cases and 723,100 deaths were reported in 2012. Approximately 40% of gastric cancer cases occur in China, and many are diagnosed at an advanced stage with a tendency toward metastasis and recurrence [4]. Peritoneal carcinoma occurs in both the advanced and early stages of gastric cancer and is the most common type of metastasis and recurrence [5–7].…”

Section: Introductionmentioning

confidence: 99%

Whole-exome sequencing to identify somatic mutations in peritoneal metastatic gastric adenocarcinoma: A preliminary study

Liu

Zhu

et al. 2016

Oncotarget

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Peritoneal metastasis occurs in more than half of patients with unresectable or recurrent gastric cancer and is associated with the worst prognosis. The associated genomic events and pathogenesis remain ambiguous. The aim of the present study was to characterize the mutation spectrum of gastric cancer with peritoneal metastasis and provide a basis for the identification of new biomarkers and treatment targets. Matched pairs of normal gastric mucosa and peritoneal tissue and matched pairs of primary tumor and peritoneal metastasis were collected from one patient for whole-exome sequencing (WES); Sanger sequencing was employed to confirm the somatic mutations. G>A and C>T mutations were the two most frequent transversions among the somatic mutations. We confirmed 48somatic mutations in the primary site and 49 in the peritoneal site. Additionally, 25 non-synonymous somatic variations (single-nucleotide variants, SNVs) and 2 somatic insertions/deletions (INDELs) were confirmed in the primary tumor, and 30 SNVs and 5 INDELs were verified in the peritoneal metastasis. Approximately 59% of the somatic mutations were shared between the primary and metastatic site. Five genes (TP53, BAI1, THSD1, ARID2, and KIAA2022) verified in our study were also mutated at a frequency greater than 5%in the COSMIC database. We also identified 9genes (ERBB4, ZNF721, NT5E, PDE10A, CA1, NUMB, NBN, ZFYVE16, and NCAM1) that were only mutated in metastasis and are expected to become treatment targets. In conclusion, we observed that the majority of the somatic mutations in the primary site persisted in metastasis, whereas several single-nucleotide polymorphisms occurred de novo at the second site.

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“…Clinically, the risk factors for developing metachronous peritoneal carcinomatosis are advanced stage at diagnosis, right-side cancer location, infiltrative or ulcero-infiltrative carcinomas, and history of perforation and obstruction in colorectal cancer (4)(5)(6)(7), but these factors are not reliable predictors for peritoneal metastasis in individuals. Although many researchers have investigated the mechanism of peritoneal dissemination in terms of genetic variations (8)(9)(10)(11)(12)(13)(14)(15)(16)(17), common changes of gene expression in tumor progression to peritoneal metastasis have not yet been clarified.…”

mentioning

confidence: 99%

Comprehensive Analysis of Somatic Mutations in Colorectal Cancer With Peritoneal Metastasis

Ahn

Baik

Lee

2019

In Vivo

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Background: To analyze for genetic mutations which may presage peritoneal metastasis by using targeted next-generation sequencing (NGS). Materials and Methods: Formalin-fixed, paraffin-embedded primary tumor specimens were obtained from 10 patients with small obstructing colorectal cancer and peritoneal metastasis (group A) and five with large non-obstructing colorectal cancer and no recurrence (group B). DNA was extracted for the sequencing of 409 cancer genes. The distribution of genetic mutations was compared between the two groups to find genetic mutations related to peritoneal metastasis. Results: When the samples were sorted based on similarity of gene expression by hierarchical clustering analysis, the samples were well divided between the two study groups. Mutations in ATrich interactive domain-containing protein 1A (ARID1A), polycystic kidney and hepatic disease 1 (PKHD1), ubiquitin-protein ligase E3 component n-recognin 5 (UBR5), paired box 5 (PAX5), tumor protein p53 (TP53), additional sex combs like 1 (ASXL1) and androgen receptor (AR) genes were detected more frequently in group A. Conclusion: A number of somatic mutations presumed to be relevant to colorectal cancer with peritoneal metastasis were identified in our study by NGS. 447This article is freely accessible online.

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Whole genome and transcriptome sequencing of matched primary and peritoneal metastatic gastric carcinoma

Cited by 80 publications

References 28 publications

Upregulated IQUB promotes cell proliferation and migration via activating Akt/GSK3β/β‐catenin signaling pathway in breast cancer

Upregulated IQUB promotes cell proliferation and migration via activating Akt/GSK3β/β‐catenin signaling pathway in breast cancer

Whole-exome sequencing to identify somatic mutations in peritoneal metastatic gastric adenocarcinoma: A preliminary study

Comprehensive Analysis of Somatic Mutations in Colorectal Cancer With Peritoneal Metastasis

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