Colon carcinogenesis is associated with all except-
Correct Answer: None
Description: Ans. is 'None' i.e., All are involvedPathogenesis of colorectal carcinoma o The combination of molecular events that lead to colonic adenocarcinoma is heterogeneous and includes genetic and epigenetic abnormalities.o Two distinct genetic pathways have been described, both of which involve the stepwise accumulation of multiple mutations:(1) APC/I3-Catenin pathway (Adenoma-Carcinoma Sequence)o It accounts for up 80% of sporadic colon tumours.o In includes mutation of APC early in the neoplastic process.o APC protein normally binds to and promotes the degradation of 13-catenin.When both copies of the APC gene are inactivate by mutation, loss of APC function results in P-catenin accumulation.13-catenin translocates to the nucleus where it inactivates the transcription of genes, such as those encoding MYC and Cyclin DI, which promote proliferation.o This is followed by additional mutation in K-RAS, which also promote proliferation.o Neoplastic progression is also associated with mutation in other tumour suppressur genes such as those encoding SMAD2 and SMAD4, which are effectors of TGF-0 signaling.o The tumour suppressor p53 is mutated in 70-80% of colon cancers.o Expression of telomerase is also increased as lesions become more advanced.(2) Microstatellite instability pathway (DNA mismatch repair deficiency)o Mutations occumulate in microsatellite repeat, a conditions refferred to as microsettlite instability.In this, MLH-1, MSH-2 genes in early stages and TGF BAX, BRAF, TCF-4, IGF2R in late stages are involved.Stepwise mutations inpathogenesis of colorectal carcinoma (Adenoma-Carcinoma Sequence) Normal ColonMucosa at riskAdenomaCarcinoma Germline or somaticmutation (first Hit)Methylation abnormalities,Inactivation of normal allelesProtooncogenemutation Protooncogene Additionalmutation mutationsAPC geneAPC -catenink-RAS p-53, LOHTelomerase (SMAD 2 & 4) Early involvement Late involvement
Category:
Pathology
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