The CHEK2 I157T Variant and Colorectal Cancer Susceptibility: A Systematic Review and Meta-analysis

Liu, Chuan; Wang, Qingshui; Wang, Yajie

doi:10.7314/apjcp.2012.13.5.2051

Cited by 62 publications

(27 citation statements)

References 35 publications

(45 reference statements)

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“…More importantly, SKP2 was found to be frequently increased in many human cancers and played an oncogenic role in tumorigenesis; inhibition of SKP2 has emerged as a promising anticancer strategy . CHEK2 is a key protein in the regulation of the G2/M cell cycle checkpoint and was discovered to be a multiorgan cancer susceptibility gene, contributing to the development of various cancers, including breast, colorectal, prostate, ovarian, thyroid and kidney cancer . ATR is an essential kinase that is activated in S phase to orchestrate the multifaceted response to DNA replication stress, ensuring the completion of DNA replication and maintaining the integrity of the genome .…”

Section: Discussionmentioning

confidence: 99%

PHD finger protein 5A promoted lung adenocarcinoma progression via alternative splicing

Mao

et al. 2019

Cancer Medicine

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Alternative splicing (AS) and the regulation of AS by splicing factors play critical roles in cancer. Plant homeodomain (PHD)–finger domain protein PHF5A, a critical splicing factor involved in AS, has been demonstrated to play an oncogenic role in glioblastoma multiforme and breast cancer, but its biological function in lung cancer remains unclear. In the present study, we systematically analyzed the biological function and clinical relevance of PHF5A in non–small cell lung cancer (NSCLC). We found that PHF5A was significantly upregulated in NSCLC tumors compared with normal tissues in both TCGA data set and tissue microarrays. Upregulation of PHF5A was negatively correlated to the overall survival (OS) of lung adenocarcinoma (LUAD) patients. Loss‐of‐function and gain‐of‐function experiments confirmed that PHF5A functioned as an oncoprotein by promoting LUAD cell proliferation, migration and invasion, inducing G0/G1 cell cycle progression and inhibiting cisplatin–induced apoptosis. RNA–seq analysis identified many essential genes whose AS was dysregulated by PHF5A, including cell cycle–associated genes such as SKP2, CHEK2, ATR and apoptosis–associated genes such as API5 and BCL2L13. Additionally, pladienolide, a small molecular inhibitor of PHF5A, inhibited LUAD cell proliferation in a dose–dependent manner and induced AS changes similar to PHF5A knockdown. In conclusion, we validated that PHF5A played an oncogenic role via AS in LUAD and suggested that PHF5A might serve as a potential drug target with a promising anticancer therapeutic effect.

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Section: Discussionmentioning

confidence: 99%

PHD finger protein 5A promoted lung adenocarcinoma progression via alternative splicing

Mao

et al. 2019

Cancer Medicine

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“…The SureselectXT Custom 3-5.9 Mb library kit (Agilent Technology, Santa Clara, CA, USA) was used for the capture and included 19 genes APC, MUTYH, BMPR1A, SMAD4, STK11, PTEN, MLH1, MSH2, MSH6, PMS2, EPCAM, CDH1 were all high risk genes. MLH3, MSH3, PMS1,AXIN2, CTNNB1,CHEK2 and MET were genes that are part of the MMR system, wnt signaling and/or were found at the time of the development of the test to have an increased but not well defined risk [24, 28, 44, 53]. Regions of 50 kb upstream and downstream of all genes and all intronic regions were included in the target region.…”

Section: Methodsmentioning

confidence: 99%

Expanding the genotype–phenotype spectrum in hereditary colorectal cancer by gene panel testing

et al. 2016

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Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel-based approaches detecting both SNVs, indels and CNVs in the same assay. We applied a panel including 19 CRC susceptibility genes to 91 individuals of six phenotypic subgroups. Targeted NGS-based sequencing of the whole gene regions including introns of the 19 genes was used. The individuals had a family history of CRC or had a phenotype consistent with a known CRC syndrome. The purpose of the study was to demonstrate the diagnostic difficulties linked to genotype-phenotype diversity and the benefits of using a gene panel. Pathogenicity classification was carried out on 46 detected variants. In total we detected sixteen pathogenic or likely pathogenic variants and 30 variants of unknown clinical significance. Four of the pathogenic or likely pathogenic variants were found in BMPR1A in patients with unexplained familial adenomatous polyposis or atypical adenomatous polyposis, which extends the genotype-phenotype spectrum for this gene. Nine patients had more than one variant remaining after the filtration, including three with truncating mutations in BMPR1A, PMS2 and AXIN2. CNVs were found in three patients, in upstream regions of SMAD4, MSH3 and CTNNB1, and one additional individual harbored a 24.2 kb duplication in CDH1 intron1.Electronic supplementary materialThe online version of this article (doi:10.1007/s10689-016-9934-0) contains supplementary material, which is available to authorized users.

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“…However, none of IVS2+1G"A and Ile157Thr mutations of CHEK2 gene was identified among the participants in the present study. Various studies showed different results regarding the relationship with other cancers: Some studies were demonstrated CHEK2 Ile157Thr variant may be one of the predisposing gene in breast and colorectal cancer susceptibility (Liu C et al, 2012 a;Liu C et al, 2012 b). Another study was conducted to evaluate the effect of CHEK2 variants and predisposition to ovarian cancer in 2006.…”

Section: Discussionmentioning

confidence: 99%

Lack of CHEK2 Gene Mutations in Differentiated Thyroid Carcinoma Patients using High Resolution Melting Analysis

Fayaz

Fard-Esfahani

Torbati³

2014

Asian Pacific Journal of Cancer Prevention

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Recently, mutations in the genes involved in cell cycle control, including CHEK2, are being considered as etiological factors in different kinds of cancers. The CHEK2 protein plays an important role in protecting damaged DNA from entering mitosis. In this study the potential effects of two common mutations IVS2+1G"A and Ile157Thr of CHEK2 gene in differentiated thyroid carcinoma (DTC) were evaluated. A total of 100 patients admitted to the Research Institute for Nuclear Medicine were diagnosed with DTC based on pathology reports of surgery samples. An additional 100 people were selected as a control group with no cancer history. PCR-HRM (high resolution melting) analysis was performed to deal with each of mutations in all case and control samples separately. During the analysis of IVS2+1G"A and Ile157Thr mutations of CHEK2 gene in the case and control groups, all the samples were identified as wild homozygote type. The finding suggests that IVS2+1G"A and Ile157Thr mutations of CHEK2 gene do not constitute a risk factor for DTC in the Iranian population. However, further studies with larger population are required to confirm the outcome.

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The CHEK2 I157T Variant and Colorectal Cancer Susceptibility: A Systematic Review and Meta-analysis

Cited by 62 publications

References 35 publications

PHD finger protein 5A promoted lung adenocarcinoma progression via alternative splicing

PHD finger protein 5A promoted lung adenocarcinoma progression via alternative splicing

Expanding the genotype–phenotype spectrum in hereditary colorectal cancer by gene panel testing

Lack of CHEK2 Gene Mutations in Differentiated Thyroid Carcinoma Patients using High Resolution Melting Analysis

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