Novel and reported APC germline mutations in Chinese patients with familial adenomatous polyposis

Zhang, Shujie; Qin, Haisong; Lv, Weigang; Luo, Shuang; Wang, Jin; Fu, Chunyun; Ma, Rui; Shen, Yiping; Chen, Shaoke; Wu, Lingqian

doi:10.1016/j.gene.2015.11.034

Cited by 11 publications

(9 citation statements)

References 20 publications

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“…2 Meaningly, it is a multifactorial disorder that comprises environmental and also genetic factors. 3,4 For the genomic location of the APC gene (Adenomatous polyposis coli), we can say that it is located at 5q21-q22 and includes 15 exons and remarkably it has a key role in the early stages of human tumorigenesis in colorectal cancer. 5 Correspondingly, its tumor suppressing function is thought to be located on the activity and also regulating process of the intracellular ␤ catenin within the transduction signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

The fluctuation of APC gene in WNT signaling with adenine deletion of adenomatous polyposis coli, is associated in colorectal cancer

Norollahi

Hamidian

Kohpar

et al. 2020

Journal of Coloproctology

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Colorectal cancer is one of the most important malignancies in the classification of gastrointestinal cancers. One of the predisposing factors at molecular level for this cancer is via WNT signaling which is associated with the vast numbers of different genes. Thus, in this study, we aimed to investigate whether Adenomatous Polyposis Coli gene (APC) mutation of rs41115in two locations such as 132.002 and 131.989 acts as a trigger or cause of colorectal cancer. Relatively, 30 blood samples of colorectal cancer patients and 30 normal blood samples as control group after colonoscopy and also confirmation of pathology report at Rohani Hospital in Babol (Iran) were investigated. The primers were designed in order to be included the rs41115 to identify the particular polymorphisms of gene. The polymerase chain reaction (PCR direct sequencing method) was used. Conclusively, deletion of adenine in two specific locations such as 131.989 and 132.002 has been identified, but there was no relationship between rs41115 polymorphisms located in adenomatous polyposis coli gene and colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

The fluctuation of APC gene in WNT signaling with adenine deletion of adenomatous polyposis coli, is associated in colorectal cancer

Norollahi

Hamidian

Kohpar

et al. 2020

Journal of Coloproctology

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“…Pathogenic germline APC mutations are mainly caused by frameshift, nonsense mutation, aberrant splicing, missense mutation, and large-fragment deletion within the APC coding sequence [7], which can lead to genome rearrangement, causing mutated or truncated APC protein. In HGMD ( http://www.hgmd.cf.ac.uk/ac ) and LOVD ( http://www.genomed.org/lovd2/home.php?select_db=APC ), more than 1100 types of APC germline mutations have been identified, covering the whole APC gene.…”

Section: Introductionmentioning

confidence: 99%

“…Liu et al [10] reported 3 novel APC mutations (c.2510C>G, c.2016_2047del, and c.3180_3184del) from 5 Chinese FAP families, which caused truncated APC protein. Zhang et al [11] identified 2 novel APC pathogenic variants (c.794_795insG/p.Val266SerfsTer11 and c.2142_2143insG/p.His715AlafsTer19) in 5 Chinese families with FAP. We recently identified a splice-acceptor site mutation c.1744-1G>A in intron 14 [12], single-nucleotide deletion-caused frameshift mutations c.3418delC (p.Pro1140Leufs*25) in exon18 [13], c.3992_3993insA (p.Thr1332Asnfs*10) in Coding DNA Sequence (CDS)15 [14], and a large-fragment deletion (exon5-exon16; c.423_8532del) [15] of APC in Chinese FAP pedigrees.…”

Section: Introductionmentioning

confidence: 99%

Adenomatous Polyposis Coli Gene Mutations in 22 Chinese Pedigrees with Familial Adenomatous Polyposis

Wang

Zhang

et al. 2019

Med Sci Monit

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Background Familial adenomatous polyposis (FAP), which has a very high tendency of progression to colorectal cancer, is mainly caused by mutations of the adenomatous polyposis coli (APC) gene. This study systematically screened the APC mutations and observed the correlation of APC mutations with clinical manifestations of FAP. Material/Methods Eighty subjects (probands and their family members of 22 FAP pedigrees) were enrolled, underwent abdominal ultrasound, computed tomography, and colonoscopic examinations, and were assessed for APC mutations between January 2010 and June 2015 at Tianjin Union Medical Center. Peripheral blood was collected from subjects, and DNA was extracted and screened for APC mutations using multiplex ligation-dependent probe amplification for large-fragment deletions or PCR-denaturing high-performance liquid chromatography with DNA sequencing for micromutations. Results Nineteen of 22 FAP pedigrees were found to have mutations of APC , and 17 types APC mutations were identified. All the mutations were heterozygosity with autosomal dominant inheritance. APC mutations included 8 caused by frameshift, 3 by aberrant splicing, 2 by missense mutation, 2 by nonsense mutation, and 2 by large-fragment deletion. Frameshift mutation was the most common type of APC mutation, and Coding DNA Sequence 15 was the most common mutation site. Five novel APC mutations, including 1 with large-fragment deletion, were identified. Conclusions We systematically screened 17 mutations of APC from 22 Chinese pedigrees with FAP. This study will broaden the spectrum of known APC germline mutations and help understand the types and distribution of APC mutations among Chinese patients with FAP.

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“…It is a tumor suppressor gene, encoding APC protein with eight subdomains. APC protein is functioning in transcriptional regulation, cell movement, and cell death by regulating the β‐catenin protein level in cytoplasm (Spier et al, ; Zhang et al, ). Hence, mutated APC protein causes presence of high level of β‐catenin protein in cytoplasm which in turn causes loss of regulation in cell division and migration and finally develops CRC (Li et al, ; Liu et al, ; Papp et al, ).…”

Section: Introductionmentioning

confidence: 99%

Targeted next‐generation sequencing approach for molecular genetic diagnosis of hereditary colorectal cancer: Identification of a novel single nucleotide germline insertion in adenomatous polyposis coli gene causes familial adenomatous polyposis

Wang

Liang

Dey

et al. 2018

Molec Gen & Gen Med

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Background Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disease which primarily manifested with developing adenomas or polyps in colon or rectum. It is caused by the germline mutations in adenomatous polyposis coli (APC) gene. Patients with FAP are usually manifested with “hundreds or even thousands” adenomas or polyps in colon or rectum. However, without proper clinical diagnosis and timely surgical interventions, colorectal adenomas, or polyps gradually increase in size and in numbers which finally leads to colorectal cancer (CRC) at the mean age of 36 years of the patient. Methods In this study, we identified a family with FAP. In this family, FAP has been diagnosed clinically based on symptoms, medical test reports, and positive family history for three generations. In order to unveil the molecular genetic consequences underlying the disease phenotype, we performed next‐generation sequencing with a customized and designed panel of genes reported to be associated with hereditary CRC. The variant identified by next‐generation sequencing has been validated by Sanger sequencing. Results A heterozygous novel insertion [c.3992_3993insA; p.Thr1332Asnfs*10] in exon 16 of APC gene has been identified. This novel insertion is cosegregated well with the FAP phenotype among all the affected members of this family. This mutation causes a frameshift by the formation of a premature stop codon which finally results in the formation of a truncated APC protein of 1,342 amino acids instead of the wild type APC protein of 2,843 amino acids. Hence, this is a loss‐of‐function mutation. This mutation was not found in unaffected family members or in normal control individuals. Conclusion Our present study emphasizes the importance of a novel approach of the gene panel‐based high‐throughput sequencing technology for easy and rapid screening for patients with FAP or CRC which will help the clinician for follow‐up and management.

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Novel and reported APC germline mutations in Chinese patients with familial adenomatous polyposis

Cited by 11 publications

References 20 publications

The fluctuation of APC gene in WNT signaling with adenine deletion of adenomatous polyposis coli, is associated in colorectal cancer

The fluctuation of APC gene in WNT signaling with adenine deletion of adenomatous polyposis coli, is associated in colorectal cancer

Adenomatous Polyposis Coli Gene Mutations in 22 Chinese Pedigrees with Familial Adenomatous Polyposis

Targeted next‐generation sequencing approach for molecular genetic diagnosis of hereditary colorectal cancer: Identification of a novel single nucleotide germline insertion in adenomatous polyposis coli gene causes familial adenomatous polyposis

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