Tumor Suppressor Genes
Tuberous sclerosis is caused by loss-of-function mutations in TSC1 or TSC2 tumor suppressor genes
Tumor Suppressor Genes (TSGs)
- Normally brake cell division, promote apoptosis, and repair DNA.
- Recessive — both alleles must be lost or inactivated (Knudson Two-Hit Hypothesis, 1971).
- Loss of function = brakes removed = unchecked proliferation.
- BRCA1/2 clinical significance: Patients with BRCA mutations respond to PARP inhibitors (olaparib) — concept of synthetic lethality.
Read this in Cancer Pharmacology: Cell Cycle, Oncogenes & Drug Targets
What our notes say
- Tuberous sclerosis is caused by loss-of-function mutations in TSC1 or TSC2 tumor suppressor genes (Urinary Tract Obstruction & Hydronephrosis: Causes, Symptoms)
- A tumor suppressor gene is found to be silenced by promoter hypermethylation in 70% of colorectal cancers. (ONCOPATHOLOGY - MCQs WITH EXPLANATIONS)
- The following is classified as a tumor suppressor gene: (General Pathology)
- Tumor suppressor genes – normally halt proliferation/induce apoptosis; loss of function drives cancer (e.g. p53, BRCA1/2, RB) (Pharmacology CRASH Course)
- Tumor suppressor genes (p53, Rb) — normally halt cell cycle/induce apoptosis when DNA damage detected; viral inactivation of these removes the "brakes" on proliferation (VIROLOGY SEM 3 CRASHED)
- Oncogenesis – specifically the development of a tumor through activation of oncogenes/inactivation of tumor suppressor genes (Medical Virology: Hepatitis, Viral Carcinogenesis & Oncogenic Viruses)
Study material on Tumor Suppressor Genes
- ONCOPATHOLOGY - MCQs WITH EXPLANATIONS
- TUMOR SUPPRESSOR GENES & CELL CYCLE CONTROL MCQs
- ONCOPATHOLOGY MCQ EXAMINATION HAllmarks of Cancer 1,2 &3
Practice questions on Tumor Suppressor Genes
Why must BOTH copies of a tumor suppressor gene be lost for tumor development, unlike oncogenes which require mutation of only one allele?
- Tumor suppressors are always X-linked
- The remaining normal allele can still produce functional protein
- Oncogenes have higher mutation rates
- Tumor suppressors require post-translational modification
Answer: B. This follows Knudson's two-hit hypothesis. One functional copy of a tumor suppressor gene is sufficient for normal function, so both must be lost. Oncogenes are gain-of-function mutations where one mutant copy is sufficient. ---
In the adenoma-carcinoma sequence of colon cancer, what is the significance of loss of the tumor suppressor gene on chromosome 18q?
- It occurs first in the sequence
- It occurs in the middle stages between KRAS and TP53 mutations
- It prevents all polyp formation
- It is not relevant to colon cancer
Answer: B. The multistep progression typically follows: APC loss → KRAS activation → 18q loss → TP53 loss. The 18q loss occurs in intermediate stages of progression. ---
Which tumor suppressor gene can trigger apoptosis in response to DNA damage?
- Bcl-2
- Bax
- p53
- Ras
- It acts as the "guardian of the genome" and induces pro-apoptotic proteins like Bax.
Answer: C. p53 is activated by DNA damage and can induce cell cycle arrest for repair or trigger apoptosis if damage is irreparable. It acts as the "guardian of the genome" and induces pro-apoptotic proteins like Bax. --- ---
Which tumor suppressor gene can trigger apoptosis in response to DNA damage?
- Bcl-2
- Bax
- p53
- Ras
- It acts as the "guardian of the genome" and induces pro-apoptotic proteins like Bax.
Answer: C. p53 is activated by DNA damage and can induce cell cycle arrest for repair or trigger apoptosis if damage is irreparable. It acts as the "guardian of the genome" and induces pro-apoptotic proteins like Bax. --- ---
Which tumor suppressor gene can trigger apoptosis in response to DNA damage?
- Bcl-2
- Bax
- p53
- Ras
- It acts as the "guardian of the genome" and induces pro-apoptotic proteins like Bax.
Answer: C. p53 is activated by DNA damage and can induce cell cycle arrest for repair or trigger apoptosis if damage is irreparable. It acts as the "guardian of the genome" and induces pro-apoptotic proteins like Bax. --- ---
What protein does the NF2 tumor suppressor gene produce?
- E-cadherin
- β-catenin
- Neurofibromin-2 (merlin)
- APC
- Occurs only after chronic exposure
Answer: A. The NF2 tumor suppressor gene produces neurofibromin-2 (merlin), which facilitates E-cadherin-mediated contact inhibition. ---