AIM： To detect germline mutations of MLH1, and investigate microsatellite instability and expression of MLH1 in tumor tissues of hereditary non-polyposis colorectal cancer （HNPCC） with two novel germline mutations,...AIM： To detect germline mutations of MLH1, and investigate microsatellite instability and expression of MLH1 in tumor tissues of hereditary non-polyposis colorectal cancer （HNPCC） with two novel germline mutations, and further investigate the pathobiology of the two novel mutations of MLH1. METHODS： RNA was extracted from the peripheral blood of 12 patients from 12 different families that fulfilled the Amsterdam 11 Criteria for HNPCC. Germline mutations of MLH1 were determined by RT-PCR, followed by cDNA sequencing analysis. PCR-GeneScan analysis was used to investigate microsatellite instability with a panel of five microsatellite markers （BAT26, BAT25, D5S346, D2S123 and mfd15）, along with immunohistochemical staining to detect the expression of MLH1 protein in two patients＇ tumor tissues with novel mutations. RESULTS： Three germline mutations were found in four patients, one of the mutations has previously been reported, but the other two, CGC→TGC at codon 217 of exon 8 and CCG→CTG at codon 581 of exon 16, have not been reported. The two patients＇ tumor tissues with novel mutations had high-frequency microsatellite instability that showed more than two unstable loci, and both tumors lost their MLH1 protein expression. CONCLUSION： The two novel germline mutations of MLH1 in HNPCC families i.e. CGC→TGC at codon 217 of exon 8 and CCG→CTG at codon 581 of exon 16, are very likely to have pathological significance.展开更多
BACKGROUND Lynch syndrome(LS)is an autosomal dominant hereditary disorder because of germline mutations in DNA mismatch repair genes,such as MutL homolog 1(MLH1),PMS1 homolog 2,MutS homolog 2,and MutS homolog 6.Gene m...BACKGROUND Lynch syndrome(LS)is an autosomal dominant hereditary disorder because of germline mutations in DNA mismatch repair genes,such as MutL homolog 1(MLH1),PMS1 homolog 2,MutS homolog 2,and MutS homolog 6.Gene mutations could make individuals and their families more susceptible to experiencing various malignant tumors.In Chinese,MLH1 germline mutation c.(453+1_454-1)_(545+1_546-1)del-related LS has been infrequently reported.Therefore,we report a rare LS patient with colorectal and endometrioid adenocarcinoma and describe her pedigree characteristics.CASE SUMMARY A 57-year-old female patient complained of irregular postmenopausal vaginal bleeding for 6 mo.She was diagnosed with LS,colonic malignancy,endometrioid adenocarcinoma,secondary fallopian tube malignancy,and intermyometrial leiomyomas.Then,she was treated by abdominal hysterectomy,bilateral oviduct oophorectomy,and sentinel lymph node resection.Genetic testing was performed using next-generation sequencing technology to detect the causative genetic mutations.Moreover,all her family members were offered a free genetic test,but no one accepted it.CONCLUSION No tumor relapse or metastasis was found in the patient during the 30-mo followup period.The genetic panel sequencing showed a novel pathogenic germline mutation in MLH1,c.(453+1_454-1)_(545+1_546-1)del,for LS.Moreover,cancer genetic counseling and testing are still in the initial development state in China,and maybe face numerous challenges in the further.展开更多
Introduction:Muir-Torre syndrome is a phenotypic variant of Lynch syndrome characterized by a predisposition for the development of visceral malignant disease and sebaceous gland neoplasms,and it is caused by germline...Introduction:Muir-Torre syndrome is a phenotypic variant of Lynch syndrome characterized by a predisposition for the development of visceral malignant disease and sebaceous gland neoplasms,and it is caused by germline mutations in the mismatch repair genesMSH2 andMLH1.Case presentation:The proband was a 42-year-old man who had undergone surgical resection of colorectal adenocarcinoma at 28 years.He presented with macular rashes and red papule.Histological examination of the lesion on his head revealed a sebaceoma at 37 years.Follow-up of the family history revealed that the proband’s 65-year-old mother had been highly suspected to have Lynch syndrome with colorectal cancer at 40 years of age.The proband’s daughter underwent colonoscopy because of blood in the stool at the age of 13 years,but no abnormalities were found.Discussion:We have herein reported a pathogenic missense mutation c.199G>A(p.Gly67Arg)in exon 2 ofMLH1 in patients with MTS.This mutation has been reported in patients with Lynch syndrome who have no skin tumors.However,we also found that some patients with MTS had no history of any internal malignancy or skin tumor.Our data support the idea that a hiatus of many years may pass before both elements-a sebaceous neoplasm and an internal cancer-are present in a patient,thus finally allowing the diagnosis of MTS.Conclusion:A pathogenic Lynch syndrome mutation c.199G>A in exon 2 of theMLH1 gene was found in a patient with MTS who presented with a sebaceous neoplasm.展开更多
基金the Key Project of Shanghai Medical Subjects,No.05Ⅲ004 and Shanghai Pujiang Program,No.06PJ14019
文摘AIM： To detect germline mutations of MLH1, and investigate microsatellite instability and expression of MLH1 in tumor tissues of hereditary non-polyposis colorectal cancer （HNPCC） with two novel germline mutations, and further investigate the pathobiology of the two novel mutations of MLH1. METHODS： RNA was extracted from the peripheral blood of 12 patients from 12 different families that fulfilled the Amsterdam 11 Criteria for HNPCC. Germline mutations of MLH1 were determined by RT-PCR, followed by cDNA sequencing analysis. PCR-GeneScan analysis was used to investigate microsatellite instability with a panel of five microsatellite markers （BAT26, BAT25, D5S346, D2S123 and mfd15）, along with immunohistochemical staining to detect the expression of MLH1 protein in two patients＇ tumor tissues with novel mutations. RESULTS： Three germline mutations were found in four patients, one of the mutations has previously been reported, but the other two, CGC→TGC at codon 217 of exon 8 and CCG→CTG at codon 581 of exon 16, have not been reported. The two patients＇ tumor tissues with novel mutations had high-frequency microsatellite instability that showed more than two unstable loci, and both tumors lost their MLH1 protein expression. CONCLUSION： The two novel germline mutations of MLH1 in HNPCC families i.e. CGC→TGC at codon 217 of exon 8 and CCG→CTG at codon 581 of exon 16, are very likely to have pathological significance.
基金Supported by the Natural Science Fund of Science and Technology Department,Jilin,No.20180101010JCJilin Provincial Department of Education,No.JJKH20201049KJ.
文摘BACKGROUND Lynch syndrome(LS)is an autosomal dominant hereditary disorder because of germline mutations in DNA mismatch repair genes,such as MutL homolog 1(MLH1),PMS1 homolog 2,MutS homolog 2,and MutS homolog 6.Gene mutations could make individuals and their families more susceptible to experiencing various malignant tumors.In Chinese,MLH1 germline mutation c.(453+1_454-1)_(545+1_546-1)del-related LS has been infrequently reported.Therefore,we report a rare LS patient with colorectal and endometrioid adenocarcinoma and describe her pedigree characteristics.CASE SUMMARY A 57-year-old female patient complained of irregular postmenopausal vaginal bleeding for 6 mo.She was diagnosed with LS,colonic malignancy,endometrioid adenocarcinoma,secondary fallopian tube malignancy,and intermyometrial leiomyomas.Then,she was treated by abdominal hysterectomy,bilateral oviduct oophorectomy,and sentinel lymph node resection.Genetic testing was performed using next-generation sequencing technology to detect the causative genetic mutations.Moreover,all her family members were offered a free genetic test,but no one accepted it.CONCLUSION No tumor relapse or metastasis was found in the patient during the 30-mo followup period.The genetic panel sequencing showed a novel pathogenic germline mutation in MLH1,c.(453+1_454-1)_(545+1_546-1)del,for LS.Moreover,cancer genetic counseling and testing are still in the initial development state in China,and maybe face numerous challenges in the further.
基金National Natural Science Foundation of China(Nos.31401071 and 81570960)。
文摘Introduction:Muir-Torre syndrome is a phenotypic variant of Lynch syndrome characterized by a predisposition for the development of visceral malignant disease and sebaceous gland neoplasms,and it is caused by germline mutations in the mismatch repair genesMSH2 andMLH1.Case presentation:The proband was a 42-year-old man who had undergone surgical resection of colorectal adenocarcinoma at 28 years.He presented with macular rashes and red papule.Histological examination of the lesion on his head revealed a sebaceoma at 37 years.Follow-up of the family history revealed that the proband’s 65-year-old mother had been highly suspected to have Lynch syndrome with colorectal cancer at 40 years of age.The proband’s daughter underwent colonoscopy because of blood in the stool at the age of 13 years,but no abnormalities were found.Discussion:We have herein reported a pathogenic missense mutation c.199G>A(p.Gly67Arg)in exon 2 ofMLH1 in patients with MTS.This mutation has been reported in patients with Lynch syndrome who have no skin tumors.However,we also found that some patients with MTS had no history of any internal malignancy or skin tumor.Our data support the idea that a hiatus of many years may pass before both elements-a sebaceous neoplasm and an internal cancer-are present in a patient,thus finally allowing the diagnosis of MTS.Conclusion:A pathogenic Lynch syndrome mutation c.199G>A in exon 2 of theMLH1 gene was found in a patient with MTS who presented with a sebaceous neoplasm.
