Objective:To identify the causative adenomatous polyposis coli(APC)gene defects associated with a pedigree of familial adenomatous polyposis(FAP).Methods:FAP was diagnosed based on clinical manifestations,family histo...Objective:To identify the causative adenomatous polyposis coli(APC)gene defects associated with a pedigree of familial adenomatous polyposis(FAP).Methods:FAP was diagnosed based on clinical manifestations,family history,as well as endoscopic and pathological examinations.The blood samples of the FAP pedigree members,colonic polyp patients,and normal individuals were collected.Genomic DNA was then extracted from those samples.APC mutation analysis was conducted via direct polymerase chain reaction(PCR)sequencing.Results:Three synonymous mutations and a missense mutation were found:c.5034G>A(p.Glyl678Gly),c.5465T>A(p.Vall 822Asp),c.5880G>A(p.Prol960Pro),and c.5274T>G(p.Serl758Ser)・Among them,the homozygous mutation on APC gene c.5034G>A has been reported,while the other three mutations have not been reported in the Chinese Han population.Individuals with c.5465T>A(p.Vall822ASP)missense mutation eventually suffer from colon cancer and have poor prognosis.We found no mutation in patients with simple intestinal polyp and in normal individuals.In addition,there were homozygous and heterozygous mutations in different patients from the same family.Conclusion:Three new mutations of APC gene were firstly reported in Han population.The missense mutation of c.5465T>A(p.Vall 822Asp)may be the cause of carcinogenesis in this FAP pedigree with poor prognosis.展开更多
AIM: To identify prognostic factors and to correlate APC mutations with clinical features, including extracolic manifestations. METHODS: One hundred thirty-five patients who underwent surgical procedures for familial ...AIM: To identify prognostic factors and to correlate APC mutations with clinical features, including extracolic manifestations. METHODS: One hundred thirty-five patients who underwent surgical procedures for familial adenomatous polyposis(FAP) were included. FAP was diagnosed when the number of adenomatous polyps was > 100. Data related to patient, extracoloic manifestations, cancer characteristics, operative procedure, follow up and surveillance were collected. APC mutation testing was performed in the 30 most recent patients. DNA was extracted from peripheral blood and polymerase chain reaction products using 31 primer pairs on APC gene were sequenced. A retrospective study was performed to investigate a causal relationship between prognosis and feature of patient.RESULTS: The mean age of the 51 patients with colorectal cancer(CRC) was older than that of those without CRC(30.5 vs 36.9, P = 0.002). Older individuals were more likely to have colon cancer at the time of FAP diagnosis [odds ratio, 4.75(95%CI: 1.71-13.89) and 5.91(1.76-22.12) for 40-49 years and age > 50 vs age < 30). The number of confirmed deaths was 13 and the median age at death was 40 years(range, 27 to 85 years). Ten of the deaths(76.9%) were from CRC. Another cause of two cases of death were desmoid tumors(15.4%). Development of cancer on remnant rectal or ileal mucosa after surgery was not observed. The APC mutation testing revealed 23 pathogenic mutations and one likely pathogenic mutation, among which were four novel mutations. The correlation between mutational status and clinical manifestations was investigated. Mutations that could prodict poor prognosis were at codon 1309 which located on mutation cluster region, codon 1465 and codon 1507.CONCLUSION: Identification of APC mutations should aid in the diagnosis and counseling of family members in terms of early diagnosis and management of FAP.展开更多
The APCDDI （adenomatosis polyposis coli down-regulated 1） gene is an inhibitor of the Wnt signaling pathway, and a rare mutation of this gene has been associated with hereditary hypotrichosis simplex. In this study,...The APCDDI （adenomatosis polyposis coli down-regulated 1） gene is an inhibitor of the Wnt signaling pathway, and a rare mutation of this gene has been associated with hereditary hypotrichosis simplex. In this study, the authors aimed to investigate whether common APCDD1 gene polymorphisms contribute to the development of androgenic alopecia. Patients （n = 210） with androgenic alopecia and 98 controls were investigated. SNPs （Single nucleotide polymorphisms） in the coding region of the gene were sequenced. A significant difference in genotype distribution was found for the c. 1781C/T, p.L476L SNP （rs3185480） of the APCDD1 gene. This SNP is located in exon 5 and is associated with a 3.5- and a 2.8-fold increase in risk for the development of androgenic alopecia for homozygote （CI 0.933-13.125; nominal regression P = 0.063） and heterozygote （CI 1.086-7.217; nominal regression P = 0.033） carriers, respectively. These data suggest that the rs3185480 polymorphism contributes to the development of androgenic alopecia. Protein expression experiments revealed that the polymorphism is associated with reduced APCDDI protein abundance. This reduction is likely due to altered codon usage for leucine from a preferred codon （CTC） to a rare codon （CTT）, which might influence translation efficiency and, thus, APCDDI protein level.展开更多
文摘Objective:To identify the causative adenomatous polyposis coli(APC)gene defects associated with a pedigree of familial adenomatous polyposis(FAP).Methods:FAP was diagnosed based on clinical manifestations,family history,as well as endoscopic and pathological examinations.The blood samples of the FAP pedigree members,colonic polyp patients,and normal individuals were collected.Genomic DNA was then extracted from those samples.APC mutation analysis was conducted via direct polymerase chain reaction(PCR)sequencing.Results:Three synonymous mutations and a missense mutation were found:c.5034G>A(p.Glyl678Gly),c.5465T>A(p.Vall 822Asp),c.5880G>A(p.Prol960Pro),and c.5274T>G(p.Serl758Ser)・Among them,the homozygous mutation on APC gene c.5034G>A has been reported,while the other three mutations have not been reported in the Chinese Han population.Individuals with c.5465T>A(p.Vall822ASP)missense mutation eventually suffer from colon cancer and have poor prognosis.We found no mutation in patients with simple intestinal polyp and in normal individuals.In addition,there were homozygous and heterozygous mutations in different patients from the same family.Conclusion:Three new mutations of APC gene were firstly reported in Han population.The missense mutation of c.5465T>A(p.Vall 822Asp)may be the cause of carcinogenesis in this FAP pedigree with poor prognosis.
基金Supported by Korea Research Foundation, Ministry of Sci-ence, ICT, No. 2013R1A2A1A03070986 (to Kim JC)Future Planning, the Korea Health 21 R&D Project, No. HI06C0868 and No. HI13C1750the Center for Development and Commercialization of Anti--Cancer Therapeutics, Ministry of Health and Welfare, South Korea, No. HI10C2014
文摘AIM: To identify prognostic factors and to correlate APC mutations with clinical features, including extracolic manifestations. METHODS: One hundred thirty-five patients who underwent surgical procedures for familial adenomatous polyposis(FAP) were included. FAP was diagnosed when the number of adenomatous polyps was > 100. Data related to patient, extracoloic manifestations, cancer characteristics, operative procedure, follow up and surveillance were collected. APC mutation testing was performed in the 30 most recent patients. DNA was extracted from peripheral blood and polymerase chain reaction products using 31 primer pairs on APC gene were sequenced. A retrospective study was performed to investigate a causal relationship between prognosis and feature of patient.RESULTS: The mean age of the 51 patients with colorectal cancer(CRC) was older than that of those without CRC(30.5 vs 36.9, P = 0.002). Older individuals were more likely to have colon cancer at the time of FAP diagnosis [odds ratio, 4.75(95%CI: 1.71-13.89) and 5.91(1.76-22.12) for 40-49 years and age > 50 vs age < 30). The number of confirmed deaths was 13 and the median age at death was 40 years(range, 27 to 85 years). Ten of the deaths(76.9%) were from CRC. Another cause of two cases of death were desmoid tumors(15.4%). Development of cancer on remnant rectal or ileal mucosa after surgery was not observed. The APC mutation testing revealed 23 pathogenic mutations and one likely pathogenic mutation, among which were four novel mutations. The correlation between mutational status and clinical manifestations was investigated. Mutations that could prodict poor prognosis were at codon 1309 which located on mutation cluster region, codon 1465 and codon 1507.CONCLUSION: Identification of APC mutations should aid in the diagnosis and counseling of family members in terms of early diagnosis and management of FAP.
文摘The APCDDI （adenomatosis polyposis coli down-regulated 1） gene is an inhibitor of the Wnt signaling pathway, and a rare mutation of this gene has been associated with hereditary hypotrichosis simplex. In this study, the authors aimed to investigate whether common APCDD1 gene polymorphisms contribute to the development of androgenic alopecia. Patients （n = 210） with androgenic alopecia and 98 controls were investigated. SNPs （Single nucleotide polymorphisms） in the coding region of the gene were sequenced. A significant difference in genotype distribution was found for the c. 1781C/T, p.L476L SNP （rs3185480） of the APCDD1 gene. This SNP is located in exon 5 and is associated with a 3.5- and a 2.8-fold increase in risk for the development of androgenic alopecia for homozygote （CI 0.933-13.125; nominal regression P = 0.063） and heterozygote （CI 1.086-7.217; nominal regression P = 0.033） carriers, respectively. These data suggest that the rs3185480 polymorphism contributes to the development of androgenic alopecia. Protein expression experiments revealed that the polymorphism is associated with reduced APCDDI protein abundance. This reduction is likely due to altered codon usage for leucine from a preferred codon （CTC） to a rare codon （CTT）, which might influence translation efficiency and, thus, APCDDI protein level.
