Colorectal cancer(CCR) is one of the most frequent cancers in developed countries.It poses a major public health problem and there is renewed interest in understanding the basic principles of the molecular biology of ...Colorectal cancer(CCR) is one of the most frequent cancers in developed countries.It poses a major public health problem and there is renewed interest in understanding the basic principles of the molecular biology of colorectal cancer.It has been established that sporadic CCRs can arise from at least two different carcinogenic pathways.The traditional pathway,also called the suppressor or chromosomal instability pathway,follows the Fearon and Vogelstein model and shows mutation in classical oncogenes and tumour suppressor genes,such as K-ras,adenomatous polyposis coli,deleted in colorectal cancer,or p53.Alterations in the Wnt pathway are also very common in this type of tumour.The second main colorectal carcinogenesis pathway is the mutator pathway.This pathway is present in nearly 15% of all cases of sporadic colorectal cancer.It is characterized by the presence of mutations in the microsatellite sequences caused by a defect in the DNA mismatch repair genes,mostly in hMLH1 or hMSH2.These two pathways have clear molecular differences,which will be reviewed in this article,but they also present distinct histopathological features.More strikingly,their clinical behaviours are completely different,having the "mutator" tumours a better outcome than the "suppressor" tumours.展开更多
Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western world.Tumour cells acquire the hallmarks of cancer during the carcinogenic selection proces...Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western world.Tumour cells acquire the hallmarks of cancer during the carcinogenic selection process.Cell immortality is one of the principal features acquired during this process which involves the stabilization of telomere length.It is achieved mainly,by telomerase activation.Thus,the discovery of telomeres and telomerase allowed an understanding of the mechanisms by which cells can become immortalized.Different studies have shown that tumour cells have shorter telomeres than nontumour cells and have detected telomerase activity in the majority of tumours.Survival studies have determined that telomere maintenance and telomerase activity are associated with poor prognosis.Taking into account all the results achieved by different groups,quantification and evaluation of telomerase activity and measurement of telomere length may be useful methods for additional biologic and prognostic staging of colorectal carcinoma.展开更多
基金Supported by Grants from Ministerio de Sanidad y Consumo, FIS PI080033Fundación de Investigación Médica Mutua Madrilena and RTICC RD06/0020/0021
文摘Colorectal cancer(CCR) is one of the most frequent cancers in developed countries.It poses a major public health problem and there is renewed interest in understanding the basic principles of the molecular biology of colorectal cancer.It has been established that sporadic CCRs can arise from at least two different carcinogenic pathways.The traditional pathway,also called the suppressor or chromosomal instability pathway,follows the Fearon and Vogelstein model and shows mutation in classical oncogenes and tumour suppressor genes,such as K-ras,adenomatous polyposis coli,deleted in colorectal cancer,or p53.Alterations in the Wnt pathway are also very common in this type of tumour.The second main colorectal carcinogenesis pathway is the mutator pathway.This pathway is present in nearly 15% of all cases of sporadic colorectal cancer.It is characterized by the presence of mutations in the microsatellite sequences caused by a defect in the DNA mismatch repair genes,mostly in hMLH1 or hMSH2.These two pathways have clear molecular differences,which will be reviewed in this article,but they also present distinct histopathological features.More strikingly,their clinical behaviours are completely different,having the "mutator" tumours a better outcome than the "suppressor" tumours.
基金Supported by Grants from Ministerio de Sanidad y Consumo (FIS PI080033)Fundación de Investigación Médica Mutua Madrilea,and RTICC RD06/0020/0021
文摘Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western world.Tumour cells acquire the hallmarks of cancer during the carcinogenic selection process.Cell immortality is one of the principal features acquired during this process which involves the stabilization of telomere length.It is achieved mainly,by telomerase activation.Thus,the discovery of telomeres and telomerase allowed an understanding of the mechanisms by which cells can become immortalized.Different studies have shown that tumour cells have shorter telomeres than nontumour cells and have detected telomerase activity in the majority of tumours.Survival studies have determined that telomere maintenance and telomerase activity are associated with poor prognosis.Taking into account all the results achieved by different groups,quantification and evaluation of telomerase activity and measurement of telomere length may be useful methods for additional biologic and prognostic staging of colorectal carcinoma.
