APC gene is involved in?
Ans. is 'a' i.e., Colorectal carcinoma Molecular pathogenesis of colorectal carcinoma* Two distinct genetic pathways have been described, both of which involve the stepwise accumulation of multiple mutations:1) APC/b-Catenin pathway (Adenoma-Carcinoma Sequence)# It accounts for up 80% of sporadic colon tumours. In includes mutation ofAPC early in the neoplastic process. APC protein normally binds to and promotes the degradation of b-catenin. When both copies of the APC gene are inactivate by mutation, loss of APC function results in b-catenin accumulation.# b-catenin translocates to the nucleus where it inactivates the transcription of genes, such as those encoding MYC and Cyclin D1, which promote proliferation. This is followed by additional mutation in K-RASy which also promote proliferation.# Neoplastic progression is also associated with mutation in other tumour suppressur genes such as those encoding SMAD2 and SMAD4, which are effectors of TGF-b signaling. The tumor suppressor p53 is mutated in 70-80% of colon cancers.# Expression of telomerase is also increased as lesions become more advanced.2) Microstatellite instability pathway (DNA mismatch repair deficiency)# Mutations accumulate in microsatellite repeat, a conditions referred to as microsatellite instability. In this, MLH-1, MSH-2 genes in early stages and TGF (3-RII, BAX, BRAF, TCF-4, IGF2R in late stages are involved.
Colorectal carcinoma
Gastric carcinoma
Gastric lymphoma
Esophageal adenocarcinoma
G.I.T.