Molecular Oncology — MCQs
Gastric carcinoma is associated with all of the following EXCEPT:
Which gene mutation is commonly associated with malignant melanoma?
Molecular genetic testing is used to detect all of the following except?
Which of the following is a primarily RNA based technique?
Knudson two-hit hypothesis is classically exemplified by
What is the mechanism of action of Bevacizumab?
What is the treatment for HER-2 positive trastuzumab resistant breast cancer?
Molecular genetic testing is used to detect all of the following except?
Which technique is used for protein separation based on molecular size?
A patient with recurrent abortion is diagnosed to have antiphospholipid syndrome. What will be the treatment?
Molecular Oncology Indian Medical PG Practice Questions and MCQs
Question 1: Gastric carcinoma is associated with all of the following EXCEPT:
- A. Over expression of C-met
- B. Inactivation of p53
- C. Over expression of C-erb
- D. Activation of RAS (Correct Answer)
Explanation: ***Activation of RAS*** - **RAS mutations** are relatively uncommon in gastric carcinoma compared to other gastrointestinal malignancies. While KRAS mutations can occur in approximately 10-15% of gastric cancers (particularly intestinal type), they are **far less frequent** than in **pancreatic adenocarcinoma** (~90%) or **colorectal carcinoma** (~40%). - In the context of gastric carcinoma, RAS pathway alterations are **not considered a major oncogenic driver** compared to the other molecular changes listed, making this the **LEAST characteristically associated** alteration. *Inactivation of p53* - **Inactivation of the p53 tumor suppressor gene** is one of the most frequent molecular events in gastric carcinoma, occurring in approximately **50-60% of cases**. - Loss of p53 function leads to genomic instability, uncontrolled cell proliferation, and resistance to apoptosis, contributing significantly to **tumorigenesis** and **poor prognosis**. *Over expression of C-met* - **Overexpression of C-MET**, a receptor tyrosine kinase for hepatocyte growth factor (HGF), is commonly observed in gastric carcinoma (30-40% of cases) and is strongly linked to **tumor growth**, **invasion**, and **metastasis**. - C-MET amplification and overexpression promote cell proliferation, survival, migration, and angiogenesis, making it an important **therapeutic target** in advanced gastric cancer. *Over expression of C-erb* - **Overexpression of C-erbB-2 (HER2/neu)** is found in approximately **10-20% of gastric adenocarcinomas**, particularly the intestinal type. - HER2 amplification or overexpression is a significant **prognostic and predictive biomarker**, and is specifically targeted by **trastuzumab** (Herceptin) therapy in HER2-positive advanced gastric cancer, improving survival outcomes.
Question 2: Which gene mutation is commonly associated with malignant melanoma?
- A. MYCN
- B. CDKN2A (Correct Answer)
- C. RET
- D. BRAF
Explanation: ***CDK2A*** - CDK2A mutations are implicated in malignant melanoma as they disrupt the **cell cycle regulation**, contributing to uncontrolled cell growth [1]. - Loss of CDK2A function leads to reduced **p16INK4A**, a crucial inhibitor of cyclin-dependent kinases involved in **G1/S phase transition** [1,3]. - Germline mutations of p16 (CDKN2A) are present in 25% of melanoma-prone kindreds [2], and germline mutations in CDKN2A are associated with familial forms of melanoma [3]. *RET* - RET mutations are primarily associated with **medullary thyroid carcinoma** and **multiple endocrine neoplasia type 2**, not melanoma. - It is involved in the signaling pathways but does not have a direct link to melanoma pathogenesis. *None* - Suggesting "none" misrepresents the reality that specific mutations do occur in malignant melanoma, including **CDK2A** and **BRAF**. - This option fails to recognize the importance of genetic alterations in cancer development and progression. *N-myc* - N-myc mutations are primarily associated with **neuroblastoma** and not typically linked to malignant melanoma. - In melanoma, mutations of this gene do not play a significant role in its pathophysiology compared to another tumor suppressor gene like **CDK2A**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Skin, pp. 1150-1151. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 297-298. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 305-306.
Question 3: Molecular genetic testing is used to detect all of the following except?
- A. Deletion
- B. Translocation (Correct Answer)
- C. Amplification
- D. Point mutation
Explanation: ***Translocation*** - **Translocations** are chromosomal rearrangements that were historically detected primarily by **cytogenetic methods** (karyotyping, conventional FISH), rather than by traditional molecular genetic testing methods focused on DNA sequencing [3]. - While modern molecular techniques like **RT-PCR for fusion transcripts** (e.g., BCR-ABL), **NGS-based fusion detection**, and **targeted breakpoint sequencing** can now detect translocations, the classic distinction is that translocations involve large-scale structural chromosomal changes better visualized by cytogenetics [2], [3]. - In the traditional classification, molecular genetic testing referred primarily to **sequence-based methods** (PCR, Sanger sequencing) that detect smaller-scale DNA changes rather than gross chromosomal rearrangements. *Deletion* - **Deletions** are readily detected by molecular genetic testing using PCR, Sanger sequencing, MLPA (Multiplex Ligation-dependent Probe Amplification), and NGS [5]. - These techniques identify missing DNA sequences by analyzing changes in fragment size, read depth, or absence of expected amplification products [2], [5]. *Amplification* - **Amplification** (increased gene copy number) is detected by molecular methods including **quantitative PCR (qPCR)**, **digital PCR**, and **NGS-based copy number analysis** [4]. - These techniques quantify gene copy numbers to identify amplifications like HER2 amplification in breast cancer. *Point mutation* - **Point mutations** are the primary target of classic molecular genetic testing [1]. - Detected by **Sanger sequencing**, **allele-specific PCR**, **NGS panels**, and other sequence-based methods that identify single nucleotide changes in DNA [1], [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 185. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 185-186. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 342-343. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 344. [5] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 183-184.
Question 4: Which of the following is a primarily RNA based technique?
- A. Western blotting
- B. Northern blotting (Correct Answer)
- C. Southern blotting
- D. Sanger's technique
Explanation: ***Northern blotting*** - **Northern blotting** is a molecular biology technique used to study **gene expression** by detecting specific **RNA molecules** (mRNA) in a sample. - It involves separating RNA fragments by **gel electrophoresis**, transferring them to a membrane, and then detecting specific sequences using **labeled probes**. *Western blotting* - **Western blotting** is a technique used to detect specific **proteins** in a sample. - It involves separating proteins by **gel electrophoresis**, transferring them to a membrane, and then detecting specific proteins using labeled **antibodies**. *Southern blotting* - **Southern blotting** is a molecular biology method used for the detection of **specific DNA sequences** in DNA samples. - It involves separating **DNA fragments** by **gel electrophoresis**, transferring them to a membrane, and then hybridizing with a labeled probe. *Sanger's technique* - **Sanger sequencing**, or the **dideoxy chain-termination method**, is a widely used method for **DNA sequencing**. - It uses **dideoxynucleotides** to terminate DNA synthesis at specific bases, allowing the determination of the **DNA sequence**.
Question 5: Knudson two-hit hypothesis is classically exemplified by
- A. Crohn disease
- B. Ulcerative colitis
- C. Retinoblastoma (Correct Answer)
- D. Melanoma
Explanation: ***Retinoblastoma*** - The **Knudson two-hit hypothesis** was **originally formulated** based on studies of **retinoblastoma** by Alfred Knudson in 1971 [1]. - It posits that **two separate mutational events** are required to inactivate **both alleles** of the **Rb tumor suppressor gene** in the same cell, leading to tumor formation [1], [2]. - This explains both **hereditary** (germline mutation + somatic mutation) and **sporadic** (two somatic mutations) forms of retinoblastoma [1], [2]. - Retinoblastoma remains the **paradigmatic example** of this hypothesis and tumor suppressor gene inactivation [2]. *Crohn disease* - This is an **inflammatory bowel disease**, not a neoplasm, with complex etiology involving genetic susceptibility, environmental factors, and immune dysregulation. - Its pathogenesis does **not follow the Knudson two-hit hypothesis**, which specifically relates to tumor suppressor gene inactivation in cancer. *Ulcerative colitis* - Similar to Crohn disease, **ulcerative colitis** is an **inflammatory bowel disease** with multifactorial etiology, not a neoplastic condition. - While chronic UC can increase colorectal cancer risk through accumulated mutations, the disease itself does **not represent the two-hit hypothesis model**. *Melanoma* - **Melanoma** is a skin cancer often linked to **UV radiation** and mutations in oncogenes like **BRAF** and tumor suppressors like **PTEN** and **CDKN2A**. [3] - While some familial melanomas involve tumor suppressor genes, melanoma is **not the classic example** used to illustrate the Knudson hypothesis—**retinoblastoma holds that distinction**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 300. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 227-228. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 297-298.
Question 6: 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 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: Molecular genetic testing is used to detect all of the following except?
- A. Translocation (Correct Answer)
- B. Point mutation
- C. Amplification
- D. Deletion
Explanation: ***Translocation*** - This is the **intended answer** for this question, based on a distinction between traditional molecular genetic testing and cytogenetic methods. - Historically, **large-scale chromosomal translocations** were primarily identified by **conventional cytogenetic methods** like **karyotyping**. - However, in modern practice, translocations **can be detected** by molecular techniques including **FISH (fluorescence in situ hybridization)**, **RT-PCR** for specific fusion genes (e.g., BCR-ABL), and **next-generation sequencing** [3], [4]. - The distinction is becoming less clear as molecular cytogenetic techniques bridge both fields. *Point mutation* - **Single nucleotide changes** (point mutations) are the **classic target** of molecular genetic testing [1]. - Readily detected by **Sanger sequencing**, **next-generation sequencing**, **PCR-based methods**, and **allele-specific assays** [3]. - These tests specifically identify alterations in individual DNA bases. *Amplification* - **Gene amplifications** (increased copy number) are routinely detected using molecular genetic techniques. - Methods include **quantitative PCR (qPCR)**, **digital PCR**, **FISH**, and **array comparative genomic hybridization (aCGH)** [2]. - Example: HER2 amplification testing in breast cancer. *Deletion* - **Deletions** ranging from single nucleotides to whole genes are readily detectable by molecular genetic testing [1]. - Techniques include **multiplex ligation-dependent probe amplification (MLPA)**, **aCGH**, **next-generation sequencing**, and **deletion-specific PCR** [2], [3]. - Small and large deletions are both within the scope of modern molecular diagnostics [1], [3]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 183-184. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 186-187. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 185-186. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 342-343.
Question 9: Which technique is used for protein separation based on molecular size?
- A. Affinity chromatography
- B. Gel filtration chromatography (Correct Answer)
- C. HPLC
- D. Salting out
Explanation: ***Gel filtration chromatography*** - Also known as **size-exclusion chromatography**, this method separates proteins by passing them through a porous matrix. **Larger proteins** elute first as they cannot enter the pores, while smaller proteins get trapped and elute later. - This technique effectively separates proteins based solely on their **hydrodynamic radius**, which is closely related to their molecular size. *Affinity chromatography* - This method separates proteins based on their **specific binding affinity** to a ligand immobilized on a stationary phase, not molecular size. - It is used for purifying proteins that bind to a specific molecule, such as an antibody or substrate. *HPLC* - **High-performance liquid chromatography** is a general technique that can use various separation mechanisms (e.g., reverse-phase, ion-exchange, size-exclusion) under high pressure. - While it *can* be used for size-exclusion, HPLC itself describes the *method* of chromatographic performance rather than a specific separation principle based on molecular size alone. *Salting out* - This technique separates proteins based on their **solubility** in high salt concentrations. - As salt concentration increases, the proteins lose their hydration shells and precipitate out of solution, with different proteins precipitating at different salt concentrations.
Question 10: A patient with recurrent abortion is diagnosed to have antiphospholipid syndrome. What will be the treatment?
- A. Aspirin alone
- B. Aspirin, Low molecular weight Heparin, and Prednisolone
- C. No treatment required
- D. Aspirin and Low molecular weight Heparin (Correct Answer)
Explanation: ***Aspirin and Low molecular weight Heparin*** - The combination of **low-dose aspirin (75-100 mg daily)** and **low molecular weight heparin (LMWH)** is the **standard of care** for pregnant women with antiphospholipid syndrome (APS) to prevent recurrent pregnancy loss. - **Aspirin** inhibits platelet aggregation and reduces thrombosis, while **LMWH** provides anticoagulation to prevent placental thrombosis and improve pregnancy outcomes. - This combination has been shown to **increase live birth rates** from approximately 40% (untreated) to **70-80%** in women with APS. *Aspirin alone* - While aspirin is part of the treatment regimen, **aspirin monotherapy is insufficient** for preventing recurrent pregnancy loss in patients with established APS. - Randomized controlled trials have demonstrated that adding heparin to aspirin **significantly improves live birth rates** compared to aspirin alone. *Aspirin, Low molecular weight Heparin, and Prednisolone* - **Corticosteroids (prednisolone)** are **not recommended** as routine treatment for recurrent pregnancy loss in APS patients due to potential maternal complications (gestational diabetes, hypertension, infection) and fetal risks. - Corticosteroids might be considered only in specific cases with coexisting autoimmune conditions (e.g., SLE), but they are **not first-line therapy** for APS-related pregnancy loss. *No treatment required* - **Antiphospholipid syndrome (APS)** is a significant cause of recurrent pregnancy loss due to placental thrombosis and impaired placental function. - **Untreated APS** carries a **high risk** (>70%) of pregnancy loss, along with increased risks of fetal growth restriction, preeclampsia, and preterm delivery, making treatment **essential** for a successful pregnancy outcome.
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