Novel APC gene mutations associated with protein alteration in diffuse type gastric cancer

Ghatak, Souvik; Chakraborty, Payel; Sarkar, S.; Chowdhury, Biswajit; Bhaumik, Arup Kumar; Kumar, Nachimuthu Senthil

doi:10.1186/s12881-017-0427-2

Cited by 22 publications

(19 citation statements)

References 42 publications

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“…CRC and GC share the same spectrum of the APC gene mutation, exons 14 and 15 are the most frequently mutated region for both cancers (Smith et al, 2002;Fornasarig et al, 2018). Ghatak et al, (2017) have demonstrated novel APC gene changes in diffuse type of GC related to cell cycle abnormalities and expression of APC protein. Tunisian patients with GC had positive APC expression in 68.7%, β-catenin in 77.5% (Ayed-Guerfali et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

Marcolino

Pimenta

Neto

et al. 2020

Asian Pac J Cancer Prev

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Colorectal cancer (CRC) is one of the most frequent neoplasms worldwide, and up to 15% have a family history. Lynch syndrome (LS) is a hereditary cause of CRC and gastric (GC). Individuals with LS have mutations in mismatch genes repair. p53, cyclin D1, β-catenin, APC and c-myc proteins are involved in the cell cycle and carcinogenesis. Objective: To study the expression of p53, Cyclin D1, β-catenin, APC and c-myc proteins in patients with CRC and GC with at least one of the Bethesda positive criteria. Compare the expression of these proteins with the presence or absence of expression of the DNA repair proteins. Patients and Methods: We included 70 individuals with CRC or GC with at least one of the Bethesda positive criteria. Protein expression of MLH1, MSH2, MSH6, PMS2, p53, cyclin D1, β-catenin, APC and c-myc were analized by immunohistochemistry tumours tissues. Results: Deficient expression of MLH1, MSH2, MSH6 and PMS2 were respectively 38.7%; 17.7%; 26.22% and 48.38%. We found a negative association between deficiency of PMS2 and age, and positive association between PMS2 deficiency and APC positive. The positive imunoexpression of APC increases by 4 times the chance of having deficiency of PMS2. Conclusions: Patients with loss of expression of PMS2 had a higher risk of mutation or deletion of APC and tumours with positive immunoexpression of cyclin D1 had an increased risk of loss of expression of MSH2. These results suggest that tumours with loss of expression of DNA repair proteins had a higher loss of cell control cycle.

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Section: Discussionmentioning

confidence: 99%

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

Marcolino

Pimenta

Neto

et al. 2020

Asian Pac J Cancer Prev

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“…APC is a tumor suppressor gene that has a key role in several molecular processes, such as suppression of canonical Wnt signaling[ 25 ], and the presence of APC mutations have been demonstrated in gastric adenocarcinoma samples[ 26 , 27 ]. APC gene mutations have been reported in both intestinal and diffuse types of gastric carcinoma with a higher frequency in the intestinal subtype of the disease[ 28 , 29 ]. The adenoma to carcinoma transition pathway has a 20% APC mutation in the intestinal type of gastric carcinoma[ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Gene mutations in stool from gastric and colorectal neoplasia patients by next-generation sequencing

Youssef

Sarhadi

Ehsan

et al. 2017

WJG

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AIMTo study cancer hotspot mutations by next-generation sequencing (NGS) in stool DNA from patients with different gastrointestinal tract (GIT) neoplasms.METHODSStool samples were collected from 87 Finnish patients diagnosed with various gastric and colorectal neoplasms, including benign tumors, and from 14 healthy controls. DNA was isolated from stools by using the PSP® Spin Stool DNA Plus Kit. For each sample, 20 ng of DNA was used to construct sequencing libraries using the Ion AmpliSeq Cancer Hotspot Panel v2 or Ion AmpliSeq Colon and Lung Cancer panel v2. Sequencing was performed on Ion PGM. Torrent Suite Software v.5.2.2 was used for variant calling and data analysis.RESULTSNGS was successful in assaying 72 GIT samples and 13 healthy controls, with success rates of the assay being 78% for stomach neoplasia and 87% for colorectal tumors. In stool specimens from patients with gastric neoplasia, five hotspot mutations were found in APC, CDKN2A and EGFR genes, in addition to seven novel mutations. From colorectal patients, 20 mutations were detected in AKT1, APC, ERBB2, FBXW7, KIT, KRAS, NRAS, SMARCB1, SMO, STK11 and TP53. Healthy controls did not exhibit any hotspot mutations, except for two novel ones. APC and TP53 were the most frequently mutated genes in colorectal neoplasms, with five mutations, followed by KRAS with two mutations. APC was the most commonly mutated gene in stools of patients with premalignant/benign GIT lesions.CONCLUSIONOur results show that in addition to colorectal neoplasms, mutations can also be assayed from stool specimens of patients with gastric neoplasms.

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“…The human adenomatous polyposis coli ( APC ) gene is located on the long (q) arm of chromosome 5, encoding a 312 kDa protein with 2,843 amino acids (Ghatak et al, 2017). APC protein is well conserved between mammals and fruit flies and well‐known as a tumor suppressor.…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have shown that most cases of colorectal cancer (CRC) are initiated by inactivation mutations in the APC gene (Tanaka et al, 2017; Yedid et al, 2016; L. Zhang & Shay, 2017). Meanwhile, gastric and colon tumors have some common genetic lesions (Ghatak et al, 2017), so it is valuable to investigate the role of the APC tumor suppressor gene in GC. Furthermore, via miRNA microarrays, we found that APC is a predictive target gene of miRNA‐192 and ‐215.…”

Section: Introductionmentioning

confidence: 99%

miRNA‐192 and ‐215 activate Wnt/β‐catenin signaling pathway in gastric cancer via APC

Deng

Zhang

Qin

et al. 2020

Journal Cellular Physiology

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Although great progress has been made in surgical techniques, traditional radiotherapy, and chemotherapy, gastric cancer (GC) is still the most common malignant tumor and has a high mortality, which highlights the importance of novel diagnostic markers. Emerging studies suggest that different microRNAs (miRNAs) are involved in tumorigenesis of GC. In this study, we found that miRNA-192 and -215 are significantly upregulated in GC and promote cell proliferation and migration. Adenomatous polyposis coli (APC), a well-known negative regulator in Wnt signaling, has been proved to be a target of miRNA-192 and -215. Inhibition of miRNA-192 or -215 reduced the Topflash activities and repressed the expression of Wnt signaling pathway proteins, while APC small interfering RNAs reversed the inhibitory effects, suggesting that miRNA-192 and -215 activate Wnt signaling via APC. In addition, APC mediates the cell proliferation and migration regulated by miRNA-192 and -215.Furthermore, APC is downregulated in GC tissues and negatively correlated with the expression of target APC and function as oncogenic miRNAs by activating Wnt signaling in GC, revealing to be potential therapeutic targets.Shiqi Deng and Xiaojing Zhang contributed equally to this study.

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Novel APC gene mutations associated with protein alteration in diffuse type gastric cancer

Cited by 22 publications

References 42 publications

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

Gene mutations in stool from gastric and colorectal neoplasia patients by next-generation sequencing

miRNA‐192 and ‐215 activate Wnt/β‐catenin signaling pathway in gastric cancer via APC

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