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
The centrosome is an organelle that serves as the microtubule-and actin-organizing center of human cells.Although the centrosome is small of size,it is great important on cellular function that regulates cytoskeletal ...The centrosome is an organelle that serves as the microtubule-and actin-organizing center of human cells.Although the centrosome is small of size,it is great important on cellular function that regulates cytoskeletal organization and governs precise spindle orientation/positioning ensuring equal distribution of cellular components in cell division.Epigenetic modifications to centrosome proteins can lead to centrosome aberrations,such as disorganized spindles and centrosome amplification causing aneuploidy and genomic instability.Epigenetic disturbances are associated not only with carcinogenesis and cancer progression,but also with drug resistance to chemotherapy.In this review,we discuss mechanisms of epigenetic alteration during the centrosome biogenesis in cancer.We provide an update on the current status of clinical trials that aim to target epigenetic modifications in centrosome aberrations and to thwart drug resistance.展开更多
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This research was funded by university of Basel, Switzerland。
文摘The centrosome is an organelle that serves as the microtubule-and actin-organizing center of human cells.Although the centrosome is small of size,it is great important on cellular function that regulates cytoskeletal organization and governs precise spindle orientation/positioning ensuring equal distribution of cellular components in cell division.Epigenetic modifications to centrosome proteins can lead to centrosome aberrations,such as disorganized spindles and centrosome amplification causing aneuploidy and genomic instability.Epigenetic disturbances are associated not only with carcinogenesis and cancer progression,but also with drug resistance to chemotherapy.In this review,we discuss mechanisms of epigenetic alteration during the centrosome biogenesis in cancer.We provide an update on the current status of clinical trials that aim to target epigenetic modifications in centrosome aberrations and to thwart drug resistance.
