-
European Journal of Cancer (Oxford,... May 2002Mutations in the adenomatous polyposis coli (APC) gene are not only responsible for familial adenomatous polyposis (FAP), but also play a rate-limiting role in the... (Review)
Review
Mutations in the adenomatous polyposis coli (APC) gene are not only responsible for familial adenomatous polyposis (FAP), but also play a rate-limiting role in the majority of sporadic colorectal cancers. Colorectal tumours are known to arise through a gradual series of histological changes, the so-called 'adenoma-carcinoma' sequence, each accompanied by a genetic alteration in a specific oncogene or tumour suppressor gene. Loss of APC function triggers this chain of molecular and histological changes. In general, an intestinal cell needs to comply with two essential requirements to develop into a cancer: it must acquire selective advantage to allow for the initial clonal expansion, and genetic instability to allow for multiple hits at other genes responsible for tumour progression and malignant transformation. Inactivation of APC seems to fulfill both requirements. In this short review, I will discuss the role played by APC in providing, when mutated, selective advantage, through constitutional activation of the Wnt signal transduction pathway, and chromosomal instability to the nascent intestinal tumor cell.
Topics: Chromosome Aberrations; Colorectal Neoplasms; Genes, APC; Homeostasis; Humans; Mutation
PubMed: 11978510
DOI: 10.1016/s0959-8049(02)00040-0 -
Nihon Rinsho. Japanese Journal of... Apr 1996The tumor suppressor gene APC is mutated in most cases of familial adenomatous polyposis (FAP) and sporadic colorectal tumors. The product of the APC gene is a 300 kDa... (Review)
Review
The tumor suppressor gene APC is mutated in most cases of familial adenomatous polyposis (FAP) and sporadic colorectal tumors. The product of the APC gene is a 300 kDa protein present in the cytoplasm as a homodimer. Interestingly, the APC protein is known to interact with the adherence junction protein catenin, suggesting that APC may be involved in cell adhesion. More recently we have demonstrated that overexpression of APC blocks cell cycle progression from the G0/G1 to the S phase.
Topics: Adenomatous Polyposis Coli; Adenomatous Polyposis Coli Protein; Cell Adhesion; Cell Cycle; Cytoskeletal Proteins; Genes, APC; Humans; Mutation
PubMed: 8920656
DOI: No ID Found -
Neoplasma 2017Colorectal cancer is the 4th most common cause of cancer related deaths worldwide and new possibilities in accurate diagnosis and targeted treatment are highly required.... (Review)
Review
Colorectal cancer is the 4th most common cause of cancer related deaths worldwide and new possibilities in accurate diagnosis and targeted treatment are highly required. Mutations in adenomatous polyposis coli (APC) gene play a pivotal role in adenoma-carcinoma pathway of colorectal tumorigenesis. The quarter century from its´ first cloning, APC became one of the most frequently mutated, known driver genes in colorectal cancer. Intensive routine molecular testing of APC has brought the benefits for patients with family history of polyposis or colorectal cancer. Nevertheless, multiple mutational disease-causing mechanisms make the genetic testing still challenging. This minireview is focused on implementation of novel APC mutation screening diagnostic strategies for polyposis families according to the current findings. A further understanding and improved algorithms may help to increase the mutation detection rate. APC germline mutations achieve close to 100% penetrance, so more comprehensive approach followed by preventive and therapeutic strategies might reflect in decrease in burden of colorectal cancer.
Topics: Adenomatous Polyposis Coli Protein; Colorectal Neoplasms; DNA Mutational Analysis; Genes, APC; Germ-Line Mutation; Humans; Mutation
PubMed: 28253712
DOI: 10.4149/neo_2017_303 -
Thoracic Cancer Nov 2021The aim of this study was to quantitatively analysis the diagnostic performance of adenomatous polyposis coli (APC) gene promoter methylation in serum or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study was to quantitatively analysis the diagnostic performance of adenomatous polyposis coli (APC) gene promoter methylation in serum or sputum/bronchoalveolar lavage fluid (BLAF) as a biomarker for lung cancer identification through pooling of open published data.
METHODS
The relevant electronic MEDLINE, EMBASE, Ovid, web of science and CNKI databases were systematically searched to identify the studies related to APC gene promoter methylation for lung cancer diagnosis. Data of true positive (tp), false positive (fp), false negative (fn) and true negative (tn) were extracted from the publications included in the study. The pooled diagnostic sensitivity, specificity and area under summary receiver operating characteristic (SROC) curve (AUC-SROC) of APC gene promoter methylation were calculated. Publication bias was evaluated by Begg's funnel plot and Egger's line regression test.
RESULTS
Fourteen studies associated with APC gene promoter methylation and lung cancer were identified in the databases and finally included in the meta-analysis. The data was pooled using a random effect model due to significant statistical heterogeneity across the 14 studies (p < 0.05). Using the APC gene promoter methylation as a reference for lung cancer identification, the pooled diagnostic sensitivity and specificity were 0.43 (95% CI: 0.40-0.45), and 0.92 (95% CI: 0.90-0.95), respectively with combined diagnostic positive likelihood ratio (+LR) and negative likelihood ratio (-LR) of 7.15 (95% CI: 3.62-14.12) and 0.63 (95% CI: 0.57-0.71). The pooled diagnostic odds ratio (DOR) and AUC-SROC of APC gene promoter methylation for lung cancer diagnosis were 9.84 (95% CI: 5.77-16.79) and 0.7, respectively. The Begg's funnel plot and Egger's line regression test both indicated statistical publication bias (t = 5.40, p < 0.05).
CONCLUSIONS
APC gene promoter methylation in serum or sputum/BLAF is a potential biomarker for lung cancer diagnosis with high specificity. However, due to its low sensitivity, it may not be suitable for lung cancer screening in the general population.
Topics: Biomarkers, Tumor; Bronchoalveolar Lavage Fluid; DNA Methylation; Early Detection of Cancer; Genes, APC; Humans; Lung Neoplasms; Sputum
PubMed: 34545707
DOI: 10.1111/1759-7714.14151 -
Progress in Experimental Tumor Research 1999
Review
Topics: Adenomatous Polyposis Coli; Animals; Disease Models, Animal; Genes, APC; Mice; Mice, Knockout
PubMed: 10377755
DOI: 10.1159/000062007 -
Gastroenterology Sep 2002
Review
Topics: Adenomatous Polyposis Coli; Cell Division; DNA Mutational Analysis; Genes, APC; Humans
PubMed: 12198717
DOI: 10.1053/gast.2002.35773 -
Bioscience Reports Mar 2020To study the correlation between adenomatous polyposis coli (APC) gene 3' untranslated region (UTR) single nucleotide polymorphisms (SNPs) and their interactions with...
OBJECTIVE
To study the correlation between adenomatous polyposis coli (APC) gene 3' untranslated region (UTR) single nucleotide polymorphisms (SNPs) and their interactions with environmental factors and the risk of colorectal cancer (CRC) in a Chinese Han population.
METHODS
Genotypes of APC gene 3'UTR rs1804197, rs41116, rs448475, and rs397768 loci in 340 Chinese Han patients with CRC and 340 healthy controls were analyzed. All patients with CRC were analyzed for progression-free survival (PFS) during a 3-year follow-up.
RESULTS
The risk of CRC in subjects carrying the APC gene rs1804197 A allele was 2.95-times higher than for the C allele carriers. The interactions of the rs1804197 SNP with body mass index (BMI) and smoking were associated with the risk of CRC. The risk of CRC in the APC gene rs397768 G allele carriers was 1.68-times higher than in the A allele carriers. The interaction between the rs397768 locus SNP and gender was also associated with the risk of CRC. The 3-year PFS of patients with APC gene rs1804197 AA genotype, CA genotype, and CC genotype CRC decreased in this order, with significant difference. In addition, the 3-year PFS of rs397768 locus GG genotype, AG genotype, and AA genotype CRC patients decreased in this order, and the difference was significant.
CONCLUSION
The rs1804197 locus in the 3'UTR region of the APC gene and its interactions with BMI and smoking are associated with the risk of CRC in a Chinese Han population. In addition, the interaction between rs397768 locus SNP and gender is related to the risk of CRC.
Topics: 3' Untranslated Regions; Adenomatous Polyposis Coli; Adult; Aged; Alleles; Asian People; Case-Control Studies; China; Colorectal Neoplasms; Epistasis, Genetic; Ethnicity; Female; Gene Frequency; Gene-Environment Interaction; Genes, APC; Genetic Predisposition to Disease; Genotype; Heterozygote; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 32159210
DOI: 10.1042/BSR20192429 -
Current Protocols in Human Genetics Jan 2017Hereditary forms of colorectal cancer (CRC) account for up to 5% of total cases. Familial adenomatous polyposis (FAP) is an autosomal dominant condition affecting nearly...
Hereditary forms of colorectal cancer (CRC) account for up to 5% of total cases. Familial adenomatous polyposis (FAP) is an autosomal dominant condition affecting nearly 1 in 5000 people and accounts for only about 1% of all CRCs. It is characterized by the progressive development of hundreds to thousands of adenomatous colon polyps. The gene associated with FAP (APC) contains 15 coding exons. The mutation spectrum of the APC gene is broad in that 87% of causative mutations are point mutations (including other sequence variants) and around 10% to 15% are intragenic deletions and duplications. The strategy for molecular diagnostic testing for FAP involves initial full sequence analysis of APC for sequence variants followed by screening for deletion/duplications using microarray-based comparative genomic hybridization (array CGH) or Multiplex Ligation-dependent Probe Amplification (MLPA). Recently, next generation sequencing (NGS)-based targeted gene analysis has become clinically available for detection of point mutations and other sequence variants. This unit discusses detailed protocols for an NGS-based sequencing assay, PCR-based Sanger sequencing, and array CGH. © 2017 by John Wiley & Sons, Inc.
Topics: Adenomatous Polyposis Coli; Comparative Genomic Hybridization; DNA Mutational Analysis; Genes, APC; High-Throughput Nucleotide Sequencing; Humans; Mutation
PubMed: 28075483
DOI: 10.1002/cphg.29 -
Current Protocols in Human Genetics Aug 2006Hereditary forms of colorectal cancer (CRC) account for up to 5% of total cases. Familial adenomatous polyposis (FAP) is an autosomal dominant condition affecting nearly... (Review)
Review
Hereditary forms of colorectal cancer (CRC) account for up to 5% of total cases. Familial adenomatous polyposis (FAP) is an autosomal dominant condition affecting nearly 1 in 5000 people and accounts for only about 1% of all CRCs. It is characterized by the progressive development of hundreds to thousands of adenomatous colon polyps. The gene associated with FAP (APC) contains 15 exons in the coding region. A scanning approach for large genes is reasonable, but some standard techniques have limited analytical sensitivity. The method described here, using DHPLC as mutation scanning approach for medium-throughput DNA sequence analysis, is largely considered to be the gold standard for point mutation analysis, and can be optimized for high-throughput testing. Detection of deletion and duplication mutations refractory to sequencing have been described using real-time quantitative PCR for dosage analysis. Technical strategies for mutation detection in the APC gene are presented in this chapter.
Topics: Adenomatous Polyposis Coli; Genes, APC; Genetic Techniques; Humans; Mutation
PubMed: 18428386
DOI: 10.1002/0471142905.hg1008s50 -
The Journal of International Medical... Aug 2022Primitive neuroectodermal tumor (PNET) of the lung is rare in adults, and treatment options vary. We herein describe the disease course and follow-up of PNET in an... (Review)
Review
Primitive neuroectodermal tumor (PNET) of the lung is rare in adults, and treatment options vary. We herein describe the disease course and follow-up of PNET in an adult. A 27-year-old man was admitted to our hospital because of cough and headache, and whole-exome sequencing revealed positive expression of the fusion gene and amplification of the gene. Although the patient received multidisciplinary treatment including chemotherapy regimens of etoposide plus cisplatin; focal radiotherapy focusing on the cerebrum, lung, and kidneys; and a subsequent palliative gastrointestinal operation, he eventually died of multiple organ functional failure. His overall survival period was 18 months, and his progression-free survival period was 4 months. During the treatment, the patient showed remarkable sensitivity to radiotherapy. In conclusion, PNET of the lung in adult patients is extremely rare, and the prognosis is very poor. Involvement of a multidisciplinary team in the development of personalized therapeutic strategies is essential. This patient with gene amplification showed excellent sensitivity to radiotherapy for intrapulmonary and intracranial lesions, suggesting that gene amplification may be related to radiotherapy sensitivity. However, further clinical research is needed.
Topics: Adult; Disease Progression; Gene Amplification; Genes, APC; Humans; Male; Neuroectodermal Tumors, Primitive; Prognosis
PubMed: 35983861
DOI: 10.1177/03000605221118704