Q.39 The event(s) that lead(s) to inactivation of tumor suppressor genes in cancer cells
is(are)
(A) gene amplification
(B) promoter methylation
(C) loss of heterozygosity
(D) histone acetylation

Promoter methylation and loss of heterozygosity inactivate tumor suppressor genes in cancer cells. Gene amplification and histone acetylation do not cause this inactivation.

Option Analysis

Gene Amplification (A)
Gene amplification increases the copy number of specific genes, typically oncogenes, promoting cancer progression. Tumor suppressor genes require loss of function, so amplification activates rather than inactivates them.

Promoter Methylation (B)
Promoter methylation adds methyl groups to CpG islands in gene promoters, blocking transcription factor binding and silencing gene expression epigenetically. This inactivates tumor suppressor genes without altering DNA sequence.

Loss of Heterozygosity (C)
Loss of heterozygosity (LOH) deletes or mutates the remaining wild-type allele of a tumor suppressor gene after one allele is inactivated, following Knudson’s two-hit hypothesis. This fully eliminates functional protein.

Histone Acetylation (D)
Histone acetylation loosens chromatin structure, enhancing gene transcription and expression. It activates genes, opposite to inactivation of tumor suppressors.

Correct options: (B) and (C).

Inactivation of tumor suppressor genes in cancer cells drives uncontrolled proliferation, a key focus for competitive exams like IIT JAM Biotechnology. These genes, such as TP53 and RB1, normally halt cell division; their silencing via specific mechanisms enables tumorigenesis. This article details promoter methylation, loss of heterozygosity, and why gene amplification or histone acetylation fail as inactivating events.

Mechanisms Explained

Promoter methylation hypermethylates CpG-rich promoters, recruiting repressive proteins and condensing chromatin to block transcription. Loss of heterozygosity erases the functional allele, fulfilling the two-hit model where both copies must be lost.

• Gene amplification boosts oncogene copies, not suppressor loss.

• Histone acetylation opens chromatin for activation, countering silencing.

Exam Relevance

For biology entrance exams, recognize (B) and (C) as correct: epigenetic silencing and genetic deletion dominate tumor suppressor inactivation. Practice distinguishes these from oncogene activation pathways.