Genetic Basis of Cancer — MCQs
A boy presents with fever, night sweats, and neck swelling. The biopsy of swelling showed a starry sky appearance. What is the most likely genetic abnormality seen in this case?
Which gene mutation is commonly associated with malignant melanoma?
Which of the following is not a tumor suppressor gene?
Which of the following childhood tumor uses N-myc gene amplification for its prognosis?
Knudson two-hit hypothesis is classically exemplified by
Which of the following conditions is least associated with tumor suppressor genes?
In which type of lung carcinoma is the p53 mutation most commonly observed?
The image below shows the life cycle of a virus. Which of the proteins of the virus act as oncogenes?
Chimney sweeper's cancer is also known as
Which enzyme is responsible for the immortality of cancer cells?
Genetic Basis of Cancer Indian Medical PG Practice Questions and MCQs
Question 1: A boy presents with fever, night sweats, and neck swelling. The biopsy of swelling showed a starry sky appearance. What is the most likely genetic abnormality seen in this case?
- A. RAS
- B. BCR-ABL
- C. p53
- D. MYC (Correct Answer)
Explanation: ***MYC*** - The clinical presentation of **fever, night sweats, and neck swelling** in a child, coupled with a **starry sky appearance** on biopsy, is highly suggestive of **Burkitt lymphoma** [2, 3]. - **Burkitt lymphoma** is characterized by a **translocation involving the *MYC* gene** on chromosome 8, most commonly t(8;14), which leads to its overexpression and uncontrolled cell proliferation [1]. *RAS* - Mutations in the **RAS family of genes (HRAS, KRAS, NRAS)** are commonly found in a wide variety of cancers, including **leukemias, pancreatic cancer, and colorectal cancer**. - While *RAS* mutations drive proliferation, they are **not the primary genetic driver** of Burkitt lymphoma, nor are they linked to the characteristic starry sky appearance. *BCR-ABL* - The **BCR-ABL fusion gene**, resulting from the **Philadelphia chromosome (t(9;22))**, is the defining genetic abnormality of **chronic myeloid leukemia (CML)**. - CML presents with different symptoms and a distinct peripheral blood and bone marrow morphology, **not the "starry sky" appearance** seen in Burkitt lymphoma. *p53* - The **p53 tumor suppressor gene** is frequently mutated or inactivated in over half of all human cancers, leading to a loss of cell cycle control and apoptosis. - While **p53 mutations can occur in aggressive lymphomas**, including Burkitt lymphoma, the **primary and characteristic genetic abnormality** associated with Burkitt lymphoma and its presentation is the *MYC* translocation, not solely *p53* mutations. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 324-325. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 605-606. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 606.
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: Which of the following is not a tumor suppressor gene?
- A. p53
- B. HER2 (Correct Answer)
- C. RB
- D. BRCA1
Explanation: ***HER2*** - **HER2** (**Human Epidermal growth factor Receptor 2**) is an **oncogene**, meaning it promotes cell growth and division when overexpressed [1]. - It is a **receptor tyrosine kinase** that, when activated, signals cells to grow and divide, and its amplification is associated with aggressive forms of breast cancer [1]. *p53* - **p53** is a well-known **tumor suppressor gene** that plays a critical role in cell cycle control and apoptosis. - It detects DNA damage and can halt cell division or initiate programmed cell death to prevent the proliferation of damaged cells. *BRCA1* - **BRCA1** (**BReast CAncer gene 1**) is a **tumor suppressor gene** involved in DNA repair. - Mutations in BRCA1 are strongly associated with increased risk of hereditary breast and ovarian cancers due to compromised DNA damage repair mechanisms. *RB* - The **retinoblastoma protein (RB)** is a classic example of a **tumor suppressor gene**. - It acts as a gatekeeper for cell cycle progression from G1 to S phase, preventing uncontrolled cell division by binding to and inactivating E2F transcription factors. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 291-294.
Question 4: Which of the following childhood tumor uses N-myc gene amplification for its prognosis?
- A. Neuroblastoma (Correct Answer)
- B. Nephroblastoma
- C. Retinoblastoma
- D. Rhabdomyosarcoma
Explanation: ***Neuroblastoma*** - **N-myc gene amplification** is a crucial **prognostic indicator** in neuroblastoma, correlating with aggressive disease and poor outcomes [1]. - Neuroblastoma is a **childhood cancer of neural crest origin**, often presenting as an adrenal mass or in sympathetic ganglia. *Nephroblastoma* - Also known as **Wilms tumor**, it is a childhood kidney cancer. - Its prognosis is more strongly associated with histology (e.g., **anaplasia**) and specific gene mutations like **WT1**, not N-myc amplification. *Retinoblastoma* - This is a **childhood eye cancer**. - Its prognosis is primarily linked to the presence of **RB1 gene mutations** and the extent of retinoblastoma gene protein (pRB) expression, not N-myc. *Rhabdomyosarcoma* - An aggressive **childhood soft tissue sarcoma** with skeletal muscle differentiation. - Prognostic factors often include clinical staging, histology (e.g., **alveolar vs. embryonal**), and specific genetic translocations like **PAX-FOXO1**, rather than N-myc amplification. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of Infancy and Childhood, pp. 486-487.
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: Which of the following conditions is least associated with tumor suppressor genes?
- A. Neurofibromatosis
- B. Retinoblastoma
- C. Acute Myeloid Leukemia (AML) (Correct Answer)
- D. Breast cancer
Explanation: ***Multiple endocrine neoplasia*** - This syndrome involves mutations in **proto-oncogenes** like RET rather than tumor suppressor genes. - The condition is mainly characterized by the presence of **multiple endocrine tumors** rather than a failure of tumor suppression. *Retinoblastoma* - Associated with mutations in the **RB1 tumor suppressor gene**, leading to uncontrolled cell proliferation [1] [2]. - Classic example of **loss of function** in a tumor suppressor gene resulting in cancer, specifically in early childhood [1] [2]. *Neurofibromatosis* - Caused by mutations in **NF1** or **NF2 genes**, both of which function as tumor suppressors. - Leads to benign tumors such as **neurofibromas** and other neurogenic tumors due to malfunction in tumor suppression. *Breast cancers* - Often related to mutations in tumor suppressor genes such as **BRCA1** and **BRCA2**, which increase cancer risk [2]. - Implicated in the hereditary form of breast and ovarian cancers due to their roles in DNA repair and cell cycle regulation [2]. **References:** [1] 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. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 298-302.
Question 7: In which type of lung carcinoma is the p53 mutation most commonly observed?
- A. Adenocarcinoma
- B. Squamous cell carcinoma (SCC) (Correct Answer)
- C. Large cell carcinoma
- D. Small cell carcinoma
Explanation: ***Small cell carcinoma*** - **Small cell lung carcinoma (SCLC)** has the highest frequency of **p53 mutations**, occurring in approximately **90-95%** of cases. - These mutations are associated with the **aggressive nature** and **poor prognosis** of SCLC, contributing to its rapid growth and early metastasis. *Adenocarcinoma* - **Adenocarcinoma** has p53 mutations in approximately **50-60%** of cases, which is less frequent than SCLC. - This subtype is more commonly associated with **EGFR mutations** and **ALK rearrangements**, particularly in non-smokers. *Squamous cell carcinoma (SCC)* - **Squamous cell carcinoma** shows p53 mutations in about **70-80%** of cases, but still lower than SCLC. - It is more strongly associated with **smoking** and often displays mutations in **CDKN2A** and **PIK3CA** pathways. *Large cell carcinoma* - **Large cell carcinoma** has variable p53 mutation rates, typically **40-60%** of cases. - This subtype is less well-characterized molecularly and represents a **diagnosis of exclusion** among lung cancers.
Question 8: The image below shows the life cycle of a virus. Which of the proteins of the virus act as oncogenes?
- A. L1, L2
- B. E1, E2, E5
- C. E1, E2
- D. E6, E7 (Correct Answer)
Explanation: ***E6, E7*** - The **E6** and **E7** proteins of high-risk human papillomaviruses (HPVs) are considered **oncogenes** because they interfere with critical tumor suppressor pathways [1][2]. - **E6** promotes the degradation of **p53**, a tumor suppressor protein, while **E7** inactivates **retinoblastoma protein (pRb)**, leading to uncontrolled cell proliferation and increased risk of malignant transformation [2]. *L1, L2* - **L1** and **L2** are **late proteins** (structural proteins) that form the **viral capsid** (outer shell) of the HPV virion. - They are essential for assembling new viral particles but do not directly contribute to the oncogenic process by disrupting host cell cycle regulation. *E1, E2, E5* - **E1** is involved in **viral DNA replication**, acting as a helicase and ATPase. - **E2** regulates **viral gene expression** and DNA replication, while **E5** is a small transmembrane protein that can contribute to cell growth but is generally considered less potent in oncogenesis than E6 and E7, and its exact role varies by HPV type. *E1, E2* - **E1** is critical for **viral DNA replication**, and **E2** regulates viral gene transcription and DNA replication. - While important for the viral life cycle, neither E1 nor E2 are the primary drivers of oncogenesis in the way E6 and E7 are, as they do not directly target key tumor suppressor proteins like p53 and pRb. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Female Genital Tract, pp. 1007-1008. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 334-335.
Question 9: Chimney sweeper's cancer is also known as
- A. Carcinoma colon
- B. Carcinoma penis
- C. Carcinoma scrotum (Correct Answer)
- D. Carcinoma lung
Explanation: ***Carcinoma scrotum*** - **Chimney Sweeper's cancer** is a historical term for **squamous cell carcinoma** of the scrotum, first described by Percivall Pott in 1775. - It was highly prevalent among chimney sweepers due to prolonged occupational exposure to **soot** (coal tar), which contains **polycyclic aromatic hydrocarbons (PAHs)**. *Carcinoma colon* - This cancer affects the **large intestine** and is linked to polyps, genetic factors, and lifestyle, not specifically soot exposure to external skin. - While PAHs can be ingested and metabolized, the direct association with "Chimney Sweeper's cancer" is specific to external skin carcinogenicity [1]. *Carcinoma penis* - This is a rare cancer associated with **HPV infection**, poor hygiene, and phimosis, primarily affecting the penile shaft or glans [2]. - It is not historically linked to occupational soot exposure in the way scrotal cancer is. *Carcinoma lung* - **Lung cancer** is strongly associated with **smoking** and exposure to airborne carcinogens like asbestos and radon, or general air pollution [1]. - While chimney sweepers might inhale soot, the term "Chimney Sweeper's cancer" specifically refers to the external **scrotal carcinoma** due to direct skin contact. **References:** [1] 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. 217-218. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lower Urinary Tract and Male Genital System, pp. 975-976.
Question 10: Which enzyme is responsible for the immortality of cancer cells?
- A. Telomerase (Correct Answer)
- B. RNA polymerase
- C. DNA reverse transcriptase
- D. DNA polymerase
Explanation: ***Telomerase*** - **Telomerase** is an enzyme that adds repetitive DNA sequences (telomeres) to the ends of chromosomes, counteracting telomere shortening that normally occurs with cell division [1]. - In cancer cells, activated telomerase prevents **telomere attrition**, allowing cells to bypass replicative senescence and achieve **immortality** [1], [2]. *DNA reverse transcriptase* - **Reverse transcriptase** synthesizes DNA from an RNA template, a process mainly found in retroviruses for replication. - While some cancer cells may activate viral pathways, DNA reverse transcriptase itself isn't the primary enzyme responsible for their intrinsic immortality. *RNA polymerase* - **RNA polymerase** is responsible for transcribing DNA into RNA, a fundamental process for gene expression and protein synthesis in all cells. - It plays a general role in cell survival and function, but not specifically in the indefinite replication characteristic of cancer cells. *DNA polymerase* - **DNA polymerase** is crucial for DNA replication and repair, ensuring the accurate duplication of genetic material during cell division. - While essential for cancer cell proliferation, it does not directly prevent telomere shortening or confer cellular immortality. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 311-312. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 312.
Want unlimited practice?
Get full access to all questions, explanations, and performance tracking.
Start For Free