Gene Therapy and Precision Medicine — MCQs
Prader-Willi syndrome and Angelman syndrome are examples of what genetic phenomenon?
CAR-T cell therapy (Chimeric Antigen Receptor T-cell therapy) is being investigated for the treatment of which malignancy?
Mutations are due to changes in:
Which of the following is the platinum-based chemotherapeutic agent used as first-line treatment for ovarian carcinoma?
What is the mechanism of action of Bevacizumab?
What is the most important tool used in genetic engineering?
What is the treatment for HER-2 positive trastuzumab resistant breast cancer?
Which of the following statements about Wilson's disease is false?
Which one of the following is an autosomal recessive disease?
Which of the following is autosomal dominant in inheritance?
Gene Therapy and Precision Medicine Indian Medical PG Practice Questions and MCQs
Question 1: Prader-Willi syndrome and Angelman syndrome are examples of what genetic phenomenon?
- A. Gene Knockout
- B. Impaired DNA repair
- C. Genomic Imprinting (Correct Answer)
- D. RNA interference
Explanation: ***Genomic Imprinting*** - **Genomic imprinting** is an epigenetic phenomenon where certain genes are expressed in a **parent-of-origin-specific manner**. - In Prader-Willi syndrome, the disease results from the loss of function of specific genes on chromosome 15 (15q11-q13) inherited from the father, while Angelman syndrome results from the loss of function of a different gene (UBE3A) in the same region, but inherited from the mother. *RNA interference* - **RNA interference** is a biological process in which RNA molecules inhibit gene expression or translation, by neutralizing targeted mRNA molecules. - This process is not directly responsible for the parent-of-origin-specific expression patterns observed in these syndromes. *Gene Knockout* - A **gene knockout** is a genetic technique in which an organism's genes are made inoperative. - While it involves modifying gene function, it does not explain the differential expression based on parental origin. *Impaired DNA repair* - **Impaired DNA repair** refers to defects in the mechanisms that correct DNA damage. - This can lead to increased mutations and conditions like cancer, but it is not the underlying mechanism for Prader-Willi or Angelman syndromes.
Question 2: CAR-T cell therapy (Chimeric Antigen Receptor T-cell therapy) is being investigated for the treatment of which malignancy?
- A. Acute Lymphoblastic Leukemia (Correct Answer)
- B. Renal Cell Carcinoma
- C. Pancreatic Cancer
- D. Glioblastoma Multiforme
Explanation: ***Acute Lymphoblastic Leukemia*** - **CAR T-cell therapy** has shown remarkable success, particularly in treating refractory or relapsed **B-cell acute lymphoblastic leukemia (ALL)** in children and young adults. - The therapy targets the **CD19 antigen** found on malignant B-cells, leading to their destruction by engineered T-cells. *Renal Cell Carcinoma* - While immune therapies are used for **renal cell carcinoma (RCC)**, traditional CAR T-cell therapy targeting specific antigens has not yet achieved widespread clinical success for this solid tumor. - RCC often presents with a **heterogeneous antigenic landscape**, making it challenging for single-target CAR T-cells. *Pancreatic Cancer* - **Pancreatic cancer** is a challenging malignancy due to its dense stroma and immunosuppressive microenvironment, which limits T-cell infiltration and efficacy. - CAR T-cell therapy for pancreatic cancer is still largely in **early-stage clinical trials**, facing significant hurdles in solid tumor treatment. *Glioblastoma Multiforme* - **Glioblastoma multiforme (GBM)** is an aggressive brain tumor with unique challenges for CAR T-cell therapy, including the **blood-brain barrier** and tumor heterogeneity. - Research is ongoing to develop CAR T-cells that can effectively target GBM, often using **regional delivery methods** or targeting multiple antigens.
Question 3: Mutations are due to changes in:
- A. DNA nucleotide sequence (Correct Answer)
- B. RNA nucleotide sequence
- C. Amino acid sequence of ribonuclease
- D. Cell membrane
Explanation: ***DNA nucleotide sequence*** - **Mutations** are defined as changes in the **genetic material**, which is primarily composed of **DNA**. - These changes in the **nucleotide sequence** of DNA can alter the genetic code, leading to changes in **protein structure and function**. *RNA nucleotide sequence* - While RNA can have its nucleotide sequence altered, these changes are generally not considered true **mutations** in the heritable sense for most organisms. - RNA is typically a temporary molecule, and changes to its sequence are usually not passed down to subsequent generations. *Amino acid sequence of ribonuclease* - An altered **amino acid sequence** in a protein like ribonuclease is a consequence of a **mutation in the DNA**, not the mutation itself. - **Ribonucleases** are enzymes that catalyze the degradation of RNA, and their structure is determined by the **DNA sequence**. *Cell membrane* - The cell membrane is a **lipid bilayer** with embedded proteins that regulates cellular transport and communication. - While its components can be affected by genetic mutations, alterations in the cell membrane itself do not constitute the primary definition of a **mutation**.
Question 4: Which of the following is the platinum-based chemotherapeutic agent used as first-line treatment for ovarian carcinoma?
- A. Cyclophosphamide
- B. Methotrexate
- C. Cisplatin (Correct Answer)
- D. Dacarbazine
Explanation: ***Cisplatin*** - **Cisplatin** is a platinum-based chemotherapy drug that forms **DNA cross-links**, inhibiting DNA synthesis and leading to the death of rapidly dividing cells, making it highly effective against **ovarian carcinoma**. - It is a cornerstone of chemotherapy regimens for ovarian cancer, often used in combination with other agents such as paclitaxel. *Methotrexate* - **Methotrexate** is an **antimetabolite** that inhibits dihydrofolate reductase, thereby interfering with DNA synthesis. - While it is used in various cancers like leukemia, lymphoma, and some solid tumors (e.g., breast cancer, gestational trophoblastic disease), it is **not a primary recommended drug for ovarian carcinoma**. *Cyclophosphamide* - **Cyclophosphamide** is an **alkylating agent** that causes DNA damage, leading to cell death. - It is used in many cancers, including lymphoma, breast cancer, and some leukemias, but it is **not a first-line or primary agent for ovarian carcinoma** in contemporary treatment guidelines. *Dacarbazine* - **Dacarbazine** is an **alkylating agent** primarily used in the treatment of **malignant melanoma** and Hodgkin lymphoma. - It is **not indicated for the treatment of ovarian carcinoma**.
Question 5: What is the mechanism of action of Bevacizumab?
- A. Anti VEGF antibody (Correct Answer)
- B. Histone deacetylase inhibitor
- C. HER2 neu inhibitor
- D. Proteasome inhibitor
Explanation: ***Anti VEGF antibody*** - **Bevacizumab** is a **monoclonal antibody** that specifically targets and binds to vascular endothelial growth factor (VEGF). - By inhibiting VEGF, bevacizumab prevents the formation of new blood vessels (**angiogenesis**) that tumors need to grow and metastasize. *Histone deacetylase inhibitor* - **Histone deacetylase (HDAC) inhibitors** influence gene expression by modifying chromatin structure, leading to cell cycle arrest and apoptosis in cancer cells. - They are used in certain hematologic malignancies and solid tumors but do not directly interfere with angiogenesis. *Proteasome inhibitor* - **Proteasome inhibitors** like bortezomib block the action of proteasomes, leading to an accumulation of ubiquitinated proteins and induction of apoptosis in cancer cells. - This mechanism is distinct from blocking new blood vessel formation. *HER2 neu inhibitor* - **HER2 neu inhibitors** (e.g., trastuzumab) specifically target the HER2/neu receptor, which is overexpressed in certain breast and gastric cancers. - Their action primarily involves blocking growth signals transmitted through this receptor, not inhibiting VEGF or angiogenesis.
Question 6: What is the most important tool used in genetic engineering?
- A. Topoisomerase
- B. DNA Ligase
- C. Restriction endonuclease (Correct Answer)
- D. Helicase
Explanation: ***Restriction endonuclease*** - **Restriction endonucleases** are crucial for genetic engineering as they specifically cut DNA at particular recognition sites, allowing the insertion or deletion of genes. - This precise cutting ability is fundamental for creating **recombinant DNA** molecules. *Helicase* - **Helicase** is primarily involved in unwinding the DNA double helix during processes like DNA replication and transcription. - While essential for cellular functions, it does not directly manipulate DNA for gene insertion or modification in the way restriction enzymes do. *Topoisomerase* - **Topoisomerase** enzymes are responsible for managing DNA supercoiling, preventing tangling during DNA replication and transcription by cutting and rejoining DNA strands. - It plays a role in DNA structure but is not directly used for targeted gene editing or insertion. *DNA Ligase* - **DNA ligase** is essential for joining DNA fragments, which is a critical step in genetic engineering after restriction endonucleases have cut the DNA. - However, while it acts as a "molecular glue" to seal nicks and re-form phosphodiester bonds, it cannot initiate the precise cutting required to isolate genes.
Question 7: What is the treatment for HER-2 positive trastuzumab resistant breast cancer?
- A. Sorafenib
- B. Lapatinib (Correct Answer)
- C. Vemurafenib
- D. Erlotinib
Explanation: ***Lapatinib*** - Lapatinib is a **dual tyrosine kinase inhibitor** that targets both **HER-2** and **epidermal growth factor receptor (EGFR)**, acting as a **small molecule inhibitor** that binds to the intracellular domain of these receptors. - Unlike trastuzumab (a monoclonal antibody targeting the extracellular domain), Lapatinib's **intracellular mechanism of action** allows it to overcome common mechanisms of trastuzumab resistance, such as receptor truncation or masking of the extracellular epitope. - It is specifically approved for the treatment of **HER-2 positive metastatic breast cancer** in combination with capecitabine after progression on trastuzumab-containing regimens. *Sorafenib* - Sorafenib is a **multi-kinase inhibitor** primarily targeting RAF, VEGFR, and PDGFR, and is used in renal cell carcinoma and hepatocellular carcinoma. - It does not specifically target HER-2 and is **not indicated** for HER-2 positive trastuzumab-resistant breast cancer. *Vemurafenib* - Vemurafenib is a **BRAF inhibitor** used for treating BRAF V600E mutation-positive melanoma. - This drug has no direct indications or demonstrated efficacy for **HER-2 positive breast cancer** and does not address trastuzumab resistance mechanisms. *Erlotinib* - Erlotinib is an **EGFR tyrosine kinase inhibitor** primarily used for non-small cell lung cancer with activating EGFR mutations. - While it targets EGFR, it does **not effectively target HER-2** and lacks the dual inhibition necessary to overcome trastuzumab resistance in HER-2 positive breast cancer.
Question 8: Which of the following statements about Wilson's disease is false?
- A. Autosomal recessive
- B. Serum ceruloplasmin level < 20 mg/dl
- C. Urinary copper excretion < 100 micrograms/day (Correct Answer)
- D. Zinc acetate is used as maintenance therapy
Explanation: ***Urinary copper excretion < 100 micrograms/day*** - A definitive diagnostic criterion for Wilson's disease is an **elevated 24-hour urinary copper excretion**, typically **greater than 100 µg/day** (or occasionally 40-100 μg/day in symptomatic patients). - Therefore, a value *less than 100 µg/day* would be considered a normal finding and would indicate that Wilson's disease is unlikely, making this statement false in the context of diagnosing the disease. *Autosomal recessive* - Wilson's disease is inherited in an **autosomal recessive pattern**, meaning an individual must inherit two copies of the mutated *ATP7B* gene (one from each parent) to develop the disease. - This characteristic inheritance pattern is fundamental to understanding the genetic basis of the disorder. *Serum ceruloplasmin level < 20 mg/dl* - **Low serum ceruloplasmin** (typically < 20 mg/dL) is a hallmark of Wilson's disease, as ceruloplasmin is the major copper-carrying protein in the blood, and its synthesis is impaired. - This low level indicates defective copper metabolism and transport, leading to copper accumulation. *Zinc acetate is used as maintenance therapy* - **Zinc acetate** (e.g., Galzin) is a commonly used maintenance therapy for Wilson's disease. - It works by inducing **metallothionein** in enterocytes, which sequesters dietary copper and prevents its absorption, thereby promoting fecal copper excretion.
Question 9: Which one of the following is an autosomal recessive disease?
- A. Retinitis pigmentosa
- B. Vitamin D resistant rickets
- C. Cystic fibrosis (Correct Answer)
- D. Neurofibromatosis
Explanation: ***Cystic fibrosis*** - **Cystic fibrosis** is caused by mutations in the **CFTR gene**, leading to defective chloride transport and thick, sticky mucus. - It is inherited in an **autosomal recessive pattern**, meaning an individual must inherit two copies of the mutated gene (one from each parent) to develop the disease. *Retinitis pigmentosa* - **Retinitis pigmentosa** is a group of inherited eye disorders, and while some forms are X-linked or autosomal dominant, a significant portion are also inherited in an **autosomal recessive pattern**. - However, it's not exclusively autosomal recessive, making cystic fibrosis a more definitive answer in this context. *Vitamin D resistant rickets* - **Vitamin D resistant rickets**, also known as **X-linked hypophosphatemic rickets**, is primarily inherited in an **X-linked dominant pattern**. - It is characterized by impaired renal phosphate reabsorption and skeletal abnormalities despite normal vitamin D levels. *Neurofibromatosis* - **Neurofibromatosis type 1 (NF1)** and **Neurofibromatosis type 2 (NF2)** are both inherited in an **autosomal dominant pattern**. - NF1 is characterized by **café-au-lait spots**, **neurofibromas**, and optical gliomas, while NF2 involves **bilateral vestibular schwannomas**.
Question 10: Which of the following is autosomal dominant in inheritance?
- A. Achondroplasia (Correct Answer)
- B. Hemochromatosis
- C. Sickle cell disease
- D. Wiskott Aldrich syndrome
Explanation: ***Achondroplasia*** - This condition is inherited in an **autosomal dominant** pattern, meaning only one copy of the mutated gene is needed to cause the disorder. - It is caused by a mutation in the **FGFR3 gene**, leading to abnormal bone growth and short-limbed dwarfism [1]. *Hemochromatosis* - This condition is primarily inherited in an **autosomal recessive** pattern, meaning two copies of the mutated gene (HFE gene) are required for the disease to manifest. - It leads to excessive iron absorption and organ damage. *Sickle cell disease* - This is an **autosomal recessive** disordertoo. - It results from a mutation in the **HBB gene**, affecting hemoglobin and causing red blood cells to become sickle-shaped. *Wiskott Aldrich syndrome* - This is an **X-linked recessive** disorder, meaning it primarily affects males. - It involves mutations in the **WAS gene**, leading to immunodeficiency, eczema, and thrombocytopenia.
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