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

Familial adenomatous polyposis (FAP) is one of the most common hereditary colorectal cancers. Its intestinal and extra-intestinal manifestations are correlated with mutation sties of the APC gene. Potential gene modulation sites in patients who have typical clinical manifestations but with unidentified APC mutations are also discussed, which included MUTYH gene, AXIN gene and certain epigenetic changes. With the generalization of Precision Medicine, to offer individualized treatment and surveillance strategy based on the genotype-phenotype correlation will be of great value for FAP patients. This review focuses on the research advance in genotype - phenotype correlation studies of FAP patients.
Adenomatous Polyposis Coli ; genetics ; Axin Protein ; genetics ; DNA Glycosylases ; genetics ; Genes, APC ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Mutation ; beta Catenin ; genetics

Serrated polyposis syndrome (SPS) is closely associated with the initiation and development of colorectal cancer (CRC), however, there is few research on SPS in China. Serrated polyps can be divided into hyperplastic polyps, sessile serrated polyps and traditional serrated polyps. The diagnosis standard of SPS is as following: (1) There are at least 5 serrated lesions in proximal colon, and diameter of more than 2 lesions is >10 mm; (2) The patient has one serrated polyp with family history of SPS; (3) More than 20 serrated polyps can be found in the entire large bowel. The risk of SPS is relatively high in the development of colorectal cancer and 25%-70% of the SPS patients is diagnosed with synchronous or metachronous colorectal cancer during following-up. The clinical characteristics of SPS include that patients are relatively old; no significant racial difference exists in the morbidity; patients have family history of colorectal cancer. The mutation of BRAF or KRAS gene, which induces colorectal cancer through the RAS-RAF-MAPK signaling pathway, is often found in SPS as well as CpG island methylation phenotype (CIMP) and microsatellite instability (MSI). The difference between SPS and traditional familial adenomatous polyposis (FAP) should be noted because of the different pathology mechanism, clinical characteristics and the risk of malignancy. Nowadays, the common technologies of detecting serrated polyps are auto-fluorescence imaging (AFI) and narrow-band imaging (NBI), whose detective rate is around 55%. The SPS patients are advised to undergo the resection of all the serrated polyps with diameter larger than 3-5 mm and receive the colonoscopy examination every 1 or 2 year. Not only the research about SPS is on the initiation step and the molecular mechanism is still unknown, but also the scholars do not come to achieve agreement about the risk of SPS in the malignancy of colorectal cancer, which is essential for further research therefore.
Adenoma ; genetics ; pathology ; therapy ; Adenomatous Polyposis Coli ; genetics ; pathology ; therapy ; Colonic Polyps ; Colonoscopy ; Colorectal Neoplasms ; genetics ; pathology ; therapy ; DNA Methylation ; Genes, ras ; Humans ; Microsatellite Instability ; Mutation ; Phenotype ; Proto-Oncogene Proteins B-raf ; Syndrome

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 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

Adenomatous Polyposis Coli ; diagnosis ; genetics ; surgery ; Colonic Neoplasms ; diagnosis ; genetics ; surgery ; Family Health ; Female ; Humans ; Male ; Middle Aged ; Pedigree ; Treatment Outcome

Adenomatous Polyposis Coli ; diagnosis ; drug therapy ; genetics ; surgery ; Antineoplastic Agents ; therapeutic use ; Colectomy ; Colorectal Neoplasms, Hereditary Nonpolyposis ; diagnosis ; drug therapy ; genetics ; surgery ; DNA Mismatch Repair ; Humans ; Ileostomy ; Peutz-Jeghers Syndrome ; diagnosis ; drug therapy ; genetics ; surgery

OBJECTIVETo study the expression of Wnt5a gene mRNA and Wnt5a, APC, β-catenin proteins in human colorectal adenocarcinoma (CRC) and explore its clinical significance.

METHODSWnt5a mRNA level was measured in 30 patients with CRC and paired non-tumor tissues by real-time PCR. Immunohistochemical staining of Wnt5a, APC, β-catenin was performed in samples of 62 patients with CRC using SP system.

RESULTSThe relative expression level of Wnt5a mRNA in fresh CRC is 0.1232 ± 0.0140, which is significantly higher than that in adjacent colorectal mucosa (0.0497 ± 0.0074, P = 0.02). A low expression of Wnt5a protein was observed in 38 of 62 CRC. Wnt5a protein expression was closely correlated with the tumor types and the degree of tumor differentiation (P < 0.05). There was no apparent relationship with lymph node metastasis, depth of myometrial invasion and TNM stages (P > 0.05). APC protein was decreased in 38 of 62 CRC. The expression of APC was closely correlated with the tumor types (P < 0.05). There was no apparent relationship with the degree of tumor differentiation, lymph node metastasis, depth of myometrial invasion and TNM stages (P > 0.05). The expression of β-catenin was observed in cytoplasm and/or cell nuclei in 50 of 62 CRC. The positive rate of β-catenin expression was closely correlated with the degree of tumor differentiation, lymph node metastasis, depth of myometrial invasion and TNM stages (P < 0.05). There was no apparent relationship with the tumor types (P > 0.05). The expressions of Wnt5a (r = 0.271, P = 0.027) and APC (r = 0.343, P = 0.004) were correlated with that of β-catenin in CRC, respectively, but there was no correlation between the expressions of Wnt5a and APC protein (r = 0.218, P = 0.078) in the tumors.

CONCLUSIONSWnt5a, APC and β-catenin genes might be involved in the carcinogenesis and development of CRC. It is hypothesized that down-regulation of APC and Wnt5a proteins may be one of causes of ectopic expression of β-catenin in CRC.

Adenocarcinoma ; metabolism ; pathology ; Adenocarcinoma, Mucinous ; metabolism ; pathology ; Adenomatous Polyposis Coli Protein ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Signet Ring Cell ; metabolism ; pathology ; Cell Differentiation ; Colorectal Neoplasms ; metabolism ; pathology ; Down-Regulation ; Female ; Genes, APC ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Proto-Oncogene Proteins ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Wnt Proteins ; genetics ; metabolism ; Wnt-5a Protein ; beta Catenin ; metabolism

Adenomatous Polyposis Coli ; genetics ; pathology ; Colonic Neoplasms ; classification ; genetics ; pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis ; diagnosis ; genetics ; DNA Glycosylases ; metabolism ; Humans ; Intestinal Polyps ; pathology ; Lymphatic Metastasis ; Neoplasm Staging ; Neuroendocrine Tumors ; classification ; pathology ; Precancerous Conditions ; pathology ; Rectal Neoplasms ; classification ; genetics ; pathology ; World Health Organization