Mutation analysis of 13 driver genes of colorectal cancer-related pathways in Taiwanese patients

Chang, Yu-Li; Chang, Jui‐Hsing; Liu, Ta Chih; Lin, Chien Yu; Yang, Shu; Ho, Cheng-Mao; Chen, William Tzu Liang; Chang, Yaotsu

doi:10.3748/wjg.v22.i7.2314

Cited by 19 publications

(17 citation statements)

References 29 publications

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“…Activation of the Wnt/β-catenin signaling pathway was shown to be one of the primary drivers of CRC development [ 21 ]. In Apc Min/+ mice, the mutations of Apc gene could activate Wnt/β-catenin signaling by preventing β-catenin degradation, which results in nuclear translocation of stabilized β-catenin and activate target gene transcription.…”

Section: Resultsmentioning

confidence: 99%

Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in ApcMin/+ Mice

et al. 2017

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Colorectal cancer (CRC) is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO) on the progression of colon carcinogenesis in ApcMin/+ mice. In addition, these effects were also investigated in HCT116 and SW480 cells. After PEO oral administration (0.2% diet) for 12 weeks, PEO significantly improved body weight changes and reduced the tumor burden and tumor multiplicity compared with the untreated mice. Meanwhile, western blot and immunohistochemistry results showed PEO significantly reduced the expression of β-catenin and cyclinD1 in both small intestine and the colon tissues compared with the untreated mice. In addition, PEO treatment significant decreased the cell viability in both HCT116 and SW480 cell lines. It also decreased the levels of β-catenin, cyclinD1, c-myc and p-GSK-3β in HCT116 and SW480 cells at 25 μM. These results indicate that PEO may have potential value in prevention of colon cancer by down-regulating Wnt-related protein.

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Section: Resultsmentioning

confidence: 99%

Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in ApcMin/+ Mice

et al. 2017

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“…One variant at splice site was also found; (Asn1209Lys) in exon 18 patient ID 3. In summary, our analysis revealed that most of investigated variants were detected in TP53 (65%) followed by ERBB2 (8.8%), suggesting more involvement of TP53 pathway than KRAS or PI3K pathways in Egyptian population [21].…”

Section: Discussionmentioning

confidence: 98%

“…Finally, two pathogenic variants were detected in PIK3CA; G>A rs104886003, Glu545Lys in patient ID 4, this mutation is one of the hotspots found in exon 10 that is considered a driver PIK3CA gene mutation [27]. Also, a known pathogenic PIK3CA mutation (A>G, rs121913279, His1047Arg) [21] was identified in patient ID 16. Therefore, most of pathogenic missense mutations were identified in KRAS in exon 2.…”

Section: Kras Pathogenic and Likely Pathogenic Variantsmentioning

confidence: 99%

“…Furthermore, exon 7 has got 2 mutations e.g. C>T, rs28934575, Gly245Ser which was previously described in CRC [20] and G>A, rs121912651, Arg248Trp which is a well-known pathogenic variant in CRC [21]. Exon 8 has got 2 pathogenic variants that are associated with Li-Fraumeni syndrome (G>A, rs149633775-Arg283Cys, C>T and rs763098116-Cys277Phe) [22].…”

Section: Pathogenic and Likely Pathogenic Variants In The Crc Cohortmentioning

confidence: 99%

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Genetic Variations of Selected Genes Using Target Deep Sequencing in Colorectal Cancer Patients

Farghal¹,

Saied²,

Ghaith³

et al. 2017

J Cancer Sci Ther

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Background: Colorectal carcinoma (CRC) is a burden problem in a developing country like Egypt since patients are usually admitted in late stage with bad prognosis and short overall survival. Because of genetic predisposition of CRC and introduction of advanced molecular techniques, efforts are directed to screen for potential pathogenic or disease-causing variants in CRC patients Methods: DNA was isolated from formalin fixed paraffin embedded tissue sections collected from 24 CRC confirmed diagnosed patients. TruSight CRC panel (Illumina) was used for detection of different variants in 15 genes. The generated reads were obtained from Illumina Miseq were clustered into single nucleotide polymorphism (SNPs) and small insertions/deletions (Indels). Further pathogenic variants with somatic and germline mutations were identified according to the recommended criteria. Some CRC patients were subjected to anti-EGFR target therapy.Results: Most of the variants were detected in TP53 gene 140 variants (65%); 105 short deletions none of them was pathogenic, 29 missense mutations and 6 SNPs at splicing sites. Next, ERBB2 has got 17 variants (8.8%) (missense and splicing), 8 of them were damaging disease causing variants. Besides, 16 pathogenic variants were identified in 12 patients (6 in TP53 and 7 in KRAS). Some pathogenic variants were not reported before in CRC e.g. TP53 C>A, rs121912654, Val157Phe. Additionally, patients carried different KRAS wild mutations showed variable response to anti-EGFR target therapy. Conclusion:The most affected pathway in CRC was TP53 pathway followed by ERBB2, NRAS, KRAS and PIK3CA genes. Variable response to target therapy suggested dependence on the type of pathogenic variant identified, also a possible role of ERBB2 which had a significant variant frequency.NRAS. The prevalence rate of TP53 mutation in Arab population is 52.5% compared to 47.5% in matched Western population [7]. TP53 mutations have roles in determining progression, invasiveness and also metastasis of CRC. So, CRC patients with mutant TP53 have more progressive phenotype and poorer survival than those with TP53 wild type [8]. The phosphatidylinositol 3-kinase/Akt/mammalian target of

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“…To gain a deeper understanding of common cancer pathways and interdependencies during tumorigenesis, we created an in silico topology based on information from databases and scientific literature to encapsulate relevant pathways in silico [38,39]. The resulting topology integrates centrally involved proteins of the common signaling pathways and generally accepted cancer drivers in CRC-such as APC, p53m, KRAS, DCC, TGFβR, PTEN and SMAD4 allowing a simplified view on the progression from normal cells to tumor cells (Table A2, Figure A8) [2,[40][41][42].…”

Section: In Silico System Responses Reflecting 3d In Vitro Data By Inmentioning

confidence: 99%

Connecting Cancer Pathways to Tumor Engines: A Stratification Tool for Colorectal Cancer Combining Human In Vitro Tissue Models with Boolean In Silico Models

Baur

Nietzer

Kunz

et al. 2019

Cancers

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To improve and focus preclinical testing, we combine tumor models based on a decellularized tissue matrix with bioinformatics to stratify tumors according to stage-specific mutations that are linked to central cancer pathways. We generated tissue models with BRAF-mutant colorectal cancer (CRC) cells (HROC24 and HROC87) and compared treatment responses to two-dimensional (2D) cultures and xenografts. As the BRAF inhibitor vemurafenib is—in contrast to melanoma—not effective in CRC, we combined it with the EGFR inhibitor gefitinib. In general, our 3D models showed higher chemoresistance and in contrast to 2D a more active HGFR after gefitinib and combination-therapy. In xenograft models murine HGF could not activate the human HGFR, stressing the importance of the human microenvironment. In order to stratify patient groups for targeted treatment options in CRC, an in silico topology with different stages including mutations and changes in common signaling pathways was developed. We applied the established topology for in silico simulations to predict new therapeutic options for BRAF-mutated CRC patients in advanced stages. Our in silico tool connects genome information with a deeper understanding of tumor engines in clinically relevant signaling networks which goes beyond the consideration of single drivers to improve CRC patient stratification.

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Mutation analysis of 13 driver genes of colorectal cancer-related pathways in Taiwanese patients

Cited by 19 publications

References 29 publications

Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in ApcMin/+ Mice

Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in ApcMin/+ Mice

Genetic Variations of Selected Genes Using Target Deep Sequencing in Colorectal Cancer Patients

Connecting Cancer Pathways to Tumor Engines: A Stratification Tool for Colorectal Cancer Combining Human In Vitro Tissue Models with Boolean In Silico Models

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