Molecular Basis of Cancer and Tumor Immunity MCQs

Activation of p53 leads to cell cycle arrest and it also directs the transcription of several pro-apoptotic genes such as BAX and PUMA which are believed to tip the balance in favour of cell death via intrinsic pathway. Reference: Robbins and Cotran Pathologic Basis of Diseases, 10 th ed, Pg: 295.

RB , a key negative regulator of the cell cycle, is directly or indirectly inactivated in most human cancers. The function of the RB protein is to regulate the G1/S checkpoint , the portal through which cells must pass before DNA replication commences. RB exerts anti-proliferative effects by controlling the G1-to-S transition of the cell cycle. Reference: Robbins and Cotran Pathologic Basis of Diseases, 10 th ed, Pg: 208-211.

UV radiation decreases its activity and causes cell cycle arrest. p53, also known as Tumor protein P53, cellular tumor antigen p53 or transformation-related protein 53 is a regulatory protein that is often mutated in human cancers. The p53 proteins are crucial in vertebrates, where they prevent cancer formation. Activated p53 promotes cell cycle arrest to allow DNA repair and/or apoptosis to prevent the propagation of cells with serious DNA damage through the transactivation of its target genes implicated in the induction of cell cycle arrest and/or apoptosis. Reference: Robbins and Cotran Pathologic Basis of Diseases, 10 th ed, Pg: 211.

All are correct except(iv). Increased transport of cyt c will cause apoptosis and killing cells thus preventing cancer. Reference: Robbins and Cotran Pathologic Basis of Diseases, 10 th ed, Pg: 217.

The tumour suppressor gene that is most commonly affected by point mutations in cancer is TP53, a prototypical "guardian" type tumour suppressor gene. DNA damage leads to activation of p53 by phosphorylation. Activated p53 drives transcription of CDKN1A(p21), which prevents RB phosphorylation, thereby causing a G1-S block in the cell cycle. This pause allows the cells to repair the DNA damage. If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, this protein prevents the cell from dividing and signals it to undergo apoptosis. By stopping cells with mutated or damaged DNA from dividing, p53 helps prevent the development of tumors. Reference: Robbins and Cotran Pathologic Basis of Diseases, 10 th Edition, Page Number 212 & 213.

Cyclin and cyclin - Dependent Kinases in regulation of cell cycle. Cyclin D/CDK4, cyclin D/CDK6 and cyclin E/CDK2 regulate G1-S transition by phosphorylation of the Rb protein. Cyclin B/CDK 1 help in G2 - M transition CDK Inhibitors ­ LNK4 inhibitors composed of p16, p15, p19 and p18 act on cyclin D/CDK 4 and cyclin D/CDK 6 p21, p27, p57, can inhibit all CDKs Reference: Robins basic pathology, 10th ed, Page: 205.

Unregulated proliferation in incipient tumours leads to telomere shortening, followed by chromosomal instability and the accumulation of mutations. If telomerase is then reactivated in these cells, telomeres are extended and these mutations become fixed, contributing to tumour growth. The telomere acts as a buffer to ensure the important genetic information coded for on the chromosome is completely copied for each new cell and protected from damage. Over time, this results in fewer and fewer DNA repeats making up the telomeres after each cell division i.e., gradually the telomeres shorten. Reference: Robbins and Cotran Pathologic Basis of Diseases, 10 th ed, Pg: 219.

This DNA repair defect increases the risk of both SCC and basal cell carcinoma Reference: Robbins & Cotran Pathologic Basis of Diseases 10 th edition Chapter 25, pg 1135