OBJECTIVE: To analyze the clinical features and genetic basis for a Chinese pedigree affected with familial adenomatous polyposis (FAP). METHODS: Clinical information of the patient was collected. Genomic DNA was extracted from peripheral blood sample of the patient and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: The proband, a 33-year-old female, was found to have multiple adenomatous polyps in the intestine. WES revealed that she has harbored a heterozygous variant of the APC gene, namely c.1922dupA (p.N641fs*10), which was unreported previously. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic. CONCLUSION The c.1922dupA (p.N641fs*10) variant of the APC gene probably underlay the FAP in this pedigree. Above finding has enabled genetic counseling for this family.
Female ; Humans ; Adult ; Pedigree ; Adenomatous Polyposis Coli Protein/genetics* ; Germ-Line Mutation ; Adenomatous Polyposis Coli/genetics* ; China ; Mutation

OBJECTIVE: To explore the genetic basis for a pedigree affected with familial adenomatous polyposis (FAP). METHODS: The proband, with recurrence of blood in the stool, was diagnosed with FAP by endoscopy, pathological examination and a family history. She was subjected to next generation sequencing to detect genetic variant. Suspected variant was verified by Sanger sequencing of members from her pedigree. RESULTS: The proband, her mother and brother were found to carry a heterozygous c.532-1G>A variant of the APC gene, which may lead to aberrant splicing of mRNA resulting in a truncated protein, which may lose its normal function and promote the tumorigenesis. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.532-1G>A variant of APC gene was predicted to be pathogenic(PVS1+PP1+PP4+PP5). CONCLUSION The c.532-1G>A variant of the APC gene probably underlay the pathogenesis of FAP in this pedigree.
Adenomatous Polyposis Coli/genetics* ; Adenomatous Polyposis Coli Protein/genetics* ; Female ; Genes, APC ; Humans ; Male ; Neoplasm Recurrence, Local ; Pedigree

OBJECTIVEThis study was aimed at establishing an efficient mutation analysis technique system to screen the germline mutations in the adenomatous polyposis coli (APC) gene that predisposes the disease susceptibility in familial adenomatous polyposis (FAP) and to investigate the relationship between genotype and phenotype of APC gene.

METHODSGenomic DNA was extracted from the peripheral blood lymphocytes of 22 patients with clinically diagnosed FAP and was forwarded to screening for germline mutations by using denaturing high-performance liquid chromatography(DHPLC), protein truncation test (PTT) and DNA sequencing in APC gene. Analysis of genotype-phenotype was also performed on the clinical data of the FAP patients.

RESULTSThirteen APC germline mutations were identified in 22 FAP patients. All of the mutations were nonsense or framshift mutations. Analysis of genotype-phenotype demonstrated that the FAP patients with mutations in the 5'or 3'extreme parts of the APC gene showed mild clinical symptoms. However, the FAP patients with mutations in the middle of the APC gene displayed typical or severe clinical symptoms.

CONCLUSIONThe technique system established in this study can efficiently and sensitively detect the mutations in APC gene. It is useful in the molecular diagnosis of pre-symptomatic FAP cases in FAP family. The clinical features of FAP patients may be related to their genotypes of APC gene.

Adenomatous Polyposis Coli ; genetics ; Adenomatous Polyposis Coli Protein ; genetics ; Chromatography, High Pressure Liquid ; DNA Mutational Analysis ; Frameshift Mutation ; genetics ; Genotype ; Germ-Line Mutation ; Humans ; Phenotype ; Polymerase Chain Reaction

OBJECTIVETo analyze the characteristics of germline mutations of adenomatous polyposis coli (APC) gene in pedigrees affected with familial adenomatous polyposis (FAP).

METHODSGenomic DNA was extracted from peripheral blood samples from members of the 13 FAP pedigrees. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large fragment deletions of the APC gene. Subsequently, potential mutation was screened from all exons of the APC gene with PCR amplification and direct sequencing.

RESULTSGermline mutations have been identified in 5 FAP pedigrees, which included c.3184_3187delCAAA, c.5432C>T, c.3925_3928delAAAA and c.3925_3929del AAAAG(in two pedigrees). Small deletional mutations were found primarily in the area of AAAAG tandem repeat sequences.

CONCLUSIONC.3925_3929 located in AAAAG tandem repeats is probably the hot spot for APC gene mutations, which are mostly deletional mutations, especially the 5 bp base deletion at codon 1309.

Adenomatous Polyposis Coli ; genetics ; Adenomatous Polyposis Coli Protein ; genetics ; Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Female ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Sequence Deletion

OBJECTIVETo analyze the mutational features of adenomatous polyposis coli (APC) gene and to explore the effect of mismatch repair (MMR) deficiency on its mutations in hereditary non-polyposis colorectal cancers (HNPCC).

METHODSPCR-based in vitro synthesized protein test (IVSP) assay and sequencing analysis were used to confirm somatic mutations of whole APC gene in 19 HNPCC patients.

RESULTSEleven cases with thirteen mutations were determined. The frequency of APC mutation was 58%(11/19). The exhibiting mutations consisted of 9 frameshift mutations and 4 nonsense ones, indicating the existence of more frameshift mutations (69%). All of frameshift mutations were deletion or insertion of 1-2 bp and most of them (7/9) happened at simple nucleotide repeat sequences, particularly within (A) n tracts (5/9). All of four nonsense mutations resulted from C to T transitions at CpG sites.

CONCLUSIONMutational inactivations of APC gene were detected in more than half of HNPCC patients in this study, indicating that APC mutation is a common molecular event in the tumorigenesis of HNPCC. According to the location of frameshift mutations at simple nucleotide repeat sequences and point mutations at CpG sites, it was suggested that endogenous mechanisms like MMR deficiency might exert an effect on the nature of APC mutations in most HNPCC.

Adenomatous Polyposis Coli ; genetics ; Adenomatous Polyposis Coli Protein ; genetics ; metabolism ; Carcinoma ; genetics ; Colorectal Neoplasms ; genetics ; pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; Genes, APC ; physiology ; Humans

OBJECTIVETo examine the distributions of beta-catenin and adenomatous polyposis coli (APC) protein in the tooth germ, and obtain the messages of function of the two factors and the relationship between them.

METHODSMice were selected and cohabited with the ratio of female mice to male ones being 2:1, and Embryo day 0.5 was confirmed based on the finding of vaginal plug. The distributions of beta-catenin and APC protein in the Embryos on day 13.5, 14.5, 15.5, 16.5, 17.5 were examined in the paraffin-embedded sections by immunohistochemistry methods.

RESULTSDuring E13.5 d to E17.5 d, positive expression of beta-catenin was found in the oral epithelium and the dental lamina, and became more and more strong. The staining were whole cell. During the bud stage, strong positive expression of APC protein was found in the oral epithelium and the dental lamina, but the expression displayed a down-regulation tendency. The staining was the cytomembrane and cytoplasm. There was negative correlation between beta-catenin and APC protein (P<0.01).

CONCLUSIONThe result of beta-catenin suggests its contribution in the early development of enamel organ and the proliferation of cell. Coincidance of the two factors staining site was found, according to the statistics.

Adenomatous Polyposis Coli Protein ; Animals ; Cytoskeletal Proteins ; Female ; Immunohistochemistry ; Male ; Mice ; Tooth Germ ; beta Catenin

OBJECTIVETo analyze mutation of adenomatous polyposis coli (APC) gene in a family affected with familial adenomatous polyposis.

METHODSThe diagnosis was made based on clinical manifestations, family history, presence of numerous polyps in the colon as well as pathological examination. Peripheral blood samples were collected, and genomic DNA was extracted. Potential mutation of the APC gene was detected by polymerase chain reaction (PCR) and DNA sequencing. After finding the mutation in the proband, the same mutation was screened among other family members. The mutation was also confirmed with PCR-restriction fragment length polymorphism (RFLP), with which 100 unrelated healthy controls were examined.

RESULTSA novel heterozygous nonsense mutation c.2891T>G (L964X) of the APC gene was identified in this pedigree. The mutation has led to premature termination of translation. The same mutation was not detected among the 100 healthy controls.

CONCLUSIONThe c.2891T>G (L964X) of the APC gene probably underlies the familial adenomatous polyposis in this pedigree. The combined DNA sequencing and PCR-RFLP method is efficient and accurate for the diagnosis.

Adenomatous Polyposis Coli ; diagnosis ; genetics ; Adenomatous Polyposis Coli Protein ; genetics ; Adult ; Base Sequence ; Child, Preschool ; Colorectal Neoplasms ; diagnosis ; genetics ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation, Missense ; Pedigree ; Point Mutation ; Young Adult

OBJECTIVETo detect the adenomatous polyposis coli (APC) gene germline mutation in the proband and her family members with familial adenomatous polyposis (FAP).

METHODSThe diagnosis of a patient with FAP was validated by colonoscopy, pathology and the family history. The systematic screening with multiplex ligation-dependent probe amplification (MLPA), denaturing high-performance liquid chromatography (DHPLC) and DNA sequencing were carried out to detect APC gene germline mutations.

RESULTSA novel mutation c.1999 C >T (Q667X) of APC, which leads to premature termination of the protein, was identified in this family. This mutation manifested an aggressive form of FAP with early onset of colorectal adenocarcinoma and colonic adenoma.

CONCLUSIONThe mutation of APC Q667X is the cause of clinical phenotype of this family with FAP, and the prophylactic colectomy for the affected family members should be considered.

Adenomatous Polyposis Coli ; genetics ; Adenomatous Polyposis Coli Protein ; genetics ; Adolescent ; Adult ; Base Sequence ; Child ; Chromatography, High Pressure Liquid ; DNA Mutational Analysis ; Female ; Germ-Line Mutation ; Humans ; Male ; Middle Aged ; Pedigree ; Phenotype ; Polymerase Chain Reaction

OBJECTIVETo investigate the expressions of Wnt-1, beta-catenin and adenomatous polyposis coli (APC) in oral squamous cell carcinoma (OSCC).

METHODSSurgical specimens from 66 OSCC patients were examined for Wnt-1, beta-catenin, APC and MIB-1 expressions by immunohistochemical staining.

RESULTSAmong all the 37 cases of well differentiated OSCCs, there were 30, 25 and 31 cases of high expressions of Wnt-1, APC and beta-catenin, respectively, 7, 12 and 6 cases of low expressions. Among all the 29 cases of moderate and poor differentiated OSCCs, there were 6, 9 and 11 cases of high expressions of Wnt-1, APC and beta-catenin respectively, 23, 20 and 18 cases of low expressions. Among all the 66 cases of OSCCs, there were 32 cases of high expressions of MIB-1 and 34 cases of low expressions. Expressions of Wnt-1, beta-catenin and APC showed significant difference in different differentiation of OSCC.

CONCLUSIONSWnt-1, beta-catenin and APC expressions were related to the differentiation of OSCC.

Adenomatous Polyposis Coli Protein ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Differentiation ; Cell Proliferation ; Humans ; Mouth Neoplasms ; metabolism ; pathology ; Signal Transduction ; Wnt1 Protein ; metabolism ; beta Catenin ; metabolism

OBJECTIVETo investigate the relationship between methylation status of APC gene in both peripheral blood and tumor tissues and clinical-pathology characteristics in patients with esophageal squamous cell carcinoma(ESCC), and to study the dynamic change of APC methylation in peripheral blood in the perioperative period.

METHODSReal-time MSP technique was used to detect methylation status of APC in tumor tissues, adjacent normal tissues and peripheral blood on the day before the surgery, intraoperative, postoperative day 7 in 76 cases with ESCC. Sixty healthy volunteers matched by age and gender were randomly selected as controls.

RESULTSThe methylation rate of APC in tumor tissue and peripheral blood was 44.74%(34/76) and 42.11%(32/76), respectively, which were significantly higher than that in adjacent normal tissue and controls [6.58%(5/76) and 1.67%(1/60), P=0.000]. The methylation rates showed good agreement between tumor tissues and peripheral blood, which could be verified by ROC curve(A Zeta=0.849, P=0.000). APC methylation rate was significantly related to pathological staging, lymph node metastasis, depth of invasion, and invasion of nerve and vessel (P<0.05). The results demonstrated that family history of cancer was independently associated with APC methylation in peripheral blood(P<0.05). DNA methylation rates in peripheral blood showed an initial increase and then decreased in the preoperative period, intraoperative and postoperative.

CONCLUSIONThe methylation rates of APC among free DNA in peripheral blood in patients with ESCC reflect tumor progression, and decrease with the solid tumour resection.

Adenomatous Polyposis Coli Protein ; metabolism ; Adult ; Aged ; Carcinoma, Squamous Cell ; blood ; metabolism ; pathology ; Case-Control Studies ; DNA Methylation ; Esophageal Neoplasms ; blood ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged