PURPOSE: APC (adenomatous polyposis coli) gene is one of the tumor-suppressor genes that acts in the early stages of cancer. Among general colon cancer patients, normal APC gene expression is deficient in 80%. It seems that APC is the most important gene in the development of colon cancer. This study was performed to analyze the mutation spectra of APC gene in sporadic colon cancer tissue from Korean patients with colon cancer. METHODS: A total of 38 patients with sporadic colon cancer were enrolled. Colon cancer tissues were analyzed for the determination of APC gene mutation spectra by multiplex ligation-dependent probe amplification (MLPA) method using SALSA MLPA P403 APC kit (MRC-Holland, Amsterdam, NL). RESULTS: APC gene mutations showing deletion/duplication in one or more exons were detected in 23 (60.5%) patients. Duplication in 13 patients (56.5%), duplication and deletion in 7 patients (30.4%), and deletion in 3 patients (13.1%) was detected. The incidence of APC gene mutation found in this study was highest in exon 3. From this study, no significant differences were observed with respect to clinicopathologic findings and the presence or absence of APC mutations. CONCLUSION: The frequency of APC gene mutation was about 61% in Korean patients with colon cancer, it showed concordance with the previous reports on the frequency of APC gene mutation from Caucasian patients with sporadic colon cancer. However, in contrast to these reports, the frequency of duplication disclosed much higher than those of western countries.
Colon ; Colonic Neoplasms ; Exons ; Genes, APC ; Humans ; Incidence ; Multiplex Polymerase Chain Reaction

Cribriform-morular variant papillary thyroid carcinoma (CMV-PTC) is a rare cancer that may arise in patients with familial adenomatous polyposis (FAP). Adenomatous polyposis coli (APC) gene mutation is associated with FAP, which is known as a premalignant lesion of colon cancer. In this report, we report a 16 years old patient of CMV-PTC comorbid with FAP, which was related with a new type of APC gene mutation.
Adenomatous Polyposis Coli ; Colonic Neoplasms ; Genes, APC ; Humans ; Thyroid Gland ; Thyroid Neoplasms

This study was aimed to investigate the efficiency of nested methylation specific polymerase chain reaction (nMS-PCR) for detecting the APC gene promoter methylation and to clarify the roles of methylation in genesis and development of hematologic malignancies, as well as to screen the hematologic malignant cell lines with hypermethylation of APC gene promoter to use as an ideal cell model for exploring the relationship between gen methylation and gene expression. The genome DNA of 10 cell lines modified with bisulfide was amplified and the methylation status of APC gene promoter was detected by using nMS-PCR. The results showed that the methylation of APC gene promoter was detected in Jurkat cells, while could not be detected in CA46, U266, Molt4, K562, HL-60, CEM, AKR, U937 and Raji cell lines. In conclusion, APC gene methylation in hematological malignant cell lines can be accurately detected by nMS-PCP method, which is simple method for detecting methylation status of various hematological malignant cell lines.
DNA Methylation ; Genes, APC ; HL-60 Cells ; Humans ; K562 Cells ; Polymerase Chain Reaction ; methods ; Promoter Regions, Genetic

OBJECTIVETo explore the clinical features and molecular mutation of early-onset familial adenomatous polyposis(FAP) in childhood.

METHODThe clinical features, endoscopic findings, pathology and therapeutic effect of sulindac during 11 years follow-up in a child with FAP were retrospectively reviewed . Adenomatous polyposis coli (APC) gene mutation analysis was performed by PCR and first generation sequencing.

RESULTThis 6-year-old girl was admitted for intermittent bloody stool during the last one and a half years. Colonoscopy showed hundreds of polyps in the rectum and colon. Pathological examination revealed tubular adenomas with high grade dysplasia. During the follow-up period of 11 years, the child presented intermittent mucous bloody stool. Endoscopy showed the number of polyps in colon and rectum increased to thousands, and found multiple polyps in gastric fundus and body.She was treated with sulindac at the age of 13. Then the number of polyps and the grade of pathology showed a slight improvement and no carcinoma was seen on biopsy. She has not accepted surgery until now. Gene sequencing of this child revealed 5 bp deletion at codon 1,309 of exon 15 (c.3927_3931delAAAGA) of tumor suppressor gene, whereas none of her parents had the same mutation. And no polyps were found on her parents colonoscopy.

CONCLUSIONThis child with FAP had an early onset of this disease, and clinical conditions were exacerbated with age. Sulindac was partially effective in controlling size and number of polyps. The site of mutation in this case was consistent with classic FAP, and without family history, the mutation may be a sporadic one.

Adenomatous Polyposis Coli ; Biopsy ; Child ; Colonoscopy ; Female ; Gastrointestinal Hemorrhage ; Genes, APC ; Humans ; Mutation ; Polymerase Chain Reaction ; Rectum ; Retrospective Studies

BACKGROUND AND OBJECTIVES: beta-catenin has an essential role in intercellular adhesion and signal transduction. The Adenomatous poliposis coli (APC) protein interacts with beta-catenin in a multi-protein complex to regulate the level of expression of beta-catenin. Mutations in beta-catenin or APC gene can lead to the accumulation of beta-catenin in the cytosol and the nucleus. This study was designed to investigate the expression of APC and beta-catenin in laryngeal cancer. SUBJECTS AND METHOD: Immunohistochemical methods were used to determine the beta-catenin and APC protein expression in 15 laryngeal cancers. Results were correlated with clinicopathological parameters. RESULTS: beta-catenin expression to the plasma membrane was reduced or absent in 11 of 15 cases (73%) of the laryngeal cancers. Cytoplasmic expression of the beta-catenin was seen in 6 out of 15 cases (40%). APC immunoactivity was negative in 5 of 15 (33%) of the laryngeal cancers. One of the six cytoplasmic expressions of the beta-catenin was negative for APC immunoactivity, and one of the five negative for APC immunoactivity was cytoplasmic expression of the beta-catenin. CONCLUSION: There was no correlation between beta-catenin and APC protein in the analysis. This finding suggests that cytoplasmic expression of the beta-catenin resulted not from the APC mutation but from the beta-catenin mutation and abnormal Wnt signal. Only the expression of the beta-catenin in cytoplasm was associated with lymph node metastasis.
beta Catenin* ; Carcinoma, Squamous Cell* ; Cell Membrane ; Cytoplasm ; Cytosol ; Genes, APC ; Laryngeal Neoplasms* ; Lymph Nodes ; Neoplasm Metastasis ; Signal Transduction

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

Colonic Polyps ; genetics ; pathology ; Colorectal Neoplasms ; genetics ; pathology ; CpG Islands ; DNA Methylation ; Genes, APC ; Genes, ras ; Humans ; Intestinal Polyps ; genetics ; pathology ; Microsatellite Repeats ; Mucin-2 ; Mucins ; analysis ; Mutation

OBJECTIVETo investigate the role of loss of heterozygosity (LOH) in tumor suppressor genes (TSG) and microsatellite instability (MSI) in hepatocarcinogenesis, as well as their correlation with clinicopathologic features.

METHODSLOH in 6 TSG (APC, DCC, MCC, OGG1, p53 and RB1) was detected in 36 informative cases of hepatocellular carcinoma (HCC), among 92 surgically resected HCC. Thirteen polymorphic microsatellite markers were also studied in 15 of these cases by microdissection-based PCR amplification and direct DNA sequencing. The correlation between genetic alterations and clinicopathologic features was analyzed.

RESULTSThe overall incidence of LOH in HCC was 41.7% (15/36). There was no LOH in MCC gene. 46.2% (6/13) microsatellites showed LOH in 9 of the 15 cases of HCC (60%). Certain clinicopathologic differences were observed between cases (number = 7) with LOH in APC, OGG1 and DCC ("type I") and cases (number = 8) with LOH in p53 and RB1 ("type II"). The mean tumor size of these two types was 2.9 (+/- 1.7) cm and 7.2 (+/- 3.4) cm, respectively (P < 0.01); and the mean survival was 72.0 (+/- 38.6) months, and 51.0 (+/- 30.4) months, respectively (P < 0.05).

CONCLUSIONSCompared with MSI pathway, LOH pathway plays a more important role in the development of HCC. A multistep hepatocarcinogenesis is likely, with LOH in APC, OGG1 and DCC ("type I") being an early event and LOH in p53 and RB1 ("type II") being a late event. On the other hand, MCC gene seems to play no role in the whole process.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; genetics ; pathology ; Female ; Genes, APC ; Genes, DCC ; Genes, MCC ; Genes, Tumor Suppressor ; Genes, p53 ; Humans ; Infant ; Liver Neoplasms ; genetics ; pathology ; Loss of Heterozygosity ; Male ; Microsatellite Instability ; Middle Aged

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 explore the characteristics of adenomatous polyposis coli (APC) gene germline mutations in Chinese patients with familial adenomatous polyposis (FAP).

METHODSEighteen members from nine FAP pedigrees were studied by using multiplex ligation-dependent probe amplification(MLPA) to detect large fragment deletion of APC gene. Then, PCR were performed to amplify all exons of APC gene for mutation screening by denaturing high performance liquid chromatography (DHPLC). When abnormal elution profile of DHPLC was found, DNA sequencing was performed to determine the mutations.

RESULTSMutations were identified in three pedigrees among the nine pedigrees. They were c.3184_3187 del CAAA in pedigree 2, c.5432C to T in pedigree 4 and c.3925_3929 del AAAAG in pedigree 9 respectively. Among them, c.5432C to T was novel.

CONCLUSIONAPC gene germline mutations can cause the development of FAP. The FAP patients without APC gene germline mutations could be caused by other mechanisms.

Adenomatous Polyposis Coli ; genetics ; Adult ; Chromatography, High Pressure Liquid ; Female ; Genes, APC ; physiology ; Genetic Predisposition to Disease ; genetics ; Germ-Line Mutation ; Humans ; Male ; Middle Aged ; Pedigree