Cancer Genetics — MCQs
Which type of thyroid cancer is associated with primary hyperparathyroidism and phaeochromocytoma?
Which gene mutation is commonly associated with malignant melanoma?
Mutations are due to changes in:
Which of the following is not a tumor suppressor gene?
A 55-year-old woman with non-small cell lung cancer is found to have an ALK gene rearrangement. How should this finding influence her treatment?
A patient presents with a skin rash that is exaggerated on sun exposure. What is the repair mechanism involved in this condition?
Which of the following is associated with defect in mismatch repair
In which type of lung carcinoma is the p53 mutation most commonly observed?
Which is not a characteristic of Li-Fraumeni syndrome?
A patient presents with headache, confusion, and a diagnosis of a brain tumor. The family history reveals brain and kidney tumors. What is the most likely diagnosis?
Cancer Genetics Indian Medical PG Practice Questions and MCQs
Question 1: Which type of thyroid cancer is associated with primary hyperparathyroidism and phaeochromocytoma?
- A. Medullary carcinoma of the thyroid (Correct Answer)
- B. Papillary carcinoma of the thyroid
- C. Anaplastic carcinoma of the thyroid
- D. Follicular carcinoma of the thyroid
Explanation: ***Medullary carcinoma of the thyroid*** - Associated with **multiple endocrine neoplasia (MEN) syndrome type 2**, which includes primary hyperparathyroidism and phaeochromocytoma [1]. - Medullary carcinoma arises from **C cells** (parafollicular cells) and is linked with **elevated calcitonin** levels. *Papillary carcinoma of the thyroid* - The most common type of thyroid cancer, but **not associated** with MEN syndromes. - Typically presents as a solitary **nodule** and is linked with **radiation exposure** rather than endocrine syndromes. *Anaplastic carcinoma of the thyroid* - A highly aggressive and undifferentiated form of thyroid cancer, often associated with **poor prognosis**. - Usually arises in older adults and does not have associations with **hyperparathyroidism** or phaeochromocytoma. *Follicular carcinoma of the thyroid* - Characterized by **thyroid follicle formation** and can be associated with **iodine deficiency**, but not with MEN syndromes. - It usually presents as a **solitary thyroid nodule** and lacks connection with **primary hyperparathyroidism**.
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: 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 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 5: A 55-year-old woman with non-small cell lung cancer is found to have an ALK gene rearrangement. How should this finding influence her treatment?
- A. Refer for surgical resection, if appropriate
- B. Switch to crizotinib, a targeted ALK inhibitor (Correct Answer)
- C. Consider radiation therapy, if indicated
- D. Continue standard chemotherapy, if appropriate for the patient's condition
Explanation: ***Switch to crizotinib, a targeted ALK inhibitor*** - The presence of an **ALK gene rearrangement** in **non-small cell lung cancer (NSCLC)** is a strong indicator for **targeted therapy** with an **ALK inhibitor** like crizotinib. - These drugs specifically block the aberrant activity of the ALK fusion protein, leading to **superior response rates** and **progression-free survival** compared to standard chemotherapy in ALK-positive patients. *Refer for surgical resection, if appropriate* - **Surgical resection** is primarily considered for **early-stage NSCLC** without evidence of metastatic disease [1]. - While surgery can be curative, the presence of specific gene rearrangements like ALK typically prompts consideration of **neoadjuvant or adjuvant targeted therapy** or systemic therapy for advanced disease. *Consider radiation therapy, if indicated* - **Radiation therapy** for NSCLC is usually employed for **local control**, either in curative intent for early stages or for **palliative management** of symptoms in advanced disease [2]. - It does not directly address the underlying **genetic driver** (ALK rearrangement) and would not be the primary systemic treatment. *Continue standard chemotherapy, if appropriate for the patient's condition* - While **standard chemotherapy** is a treatment option for NSCLC, the identification of a **driver mutation** like an ALK rearrangement makes **targeted therapy** a significantly more effective and preferred first-line approach. - Continuing chemotherapy without considering targeted therapy would be **suboptimal** for a patient with an ALK rearrangement due to the availability of more effective treatments.
Question 6: A patient presents with a skin rash that is exaggerated on sun exposure. What is the repair mechanism involved in this condition?
- A. Nucleotide excision repair (Correct Answer)
- B. Base excision repair
- C. Mismatch repair
- D. Double stranded DNA break repair
Explanation: ***Nucleotide excision repair*** - This mechanism is responsible for repairing **bulky lesions** in DNA, such as **pyrimidine dimers** caused by **UV radiation** from sun exposure. - Patients with defects in nucleotide excision repair (e.g., **xeroderma pigmentosum**) are highly sensitive to sunlight and develop skin rashes, pigment changes, and skin cancers. *Base excision repair* - This pathway primarily corrects **small damaged bases** that do not cause significant distortion of the DNA helix, such as deaminated, oxidized, or alkylated bases. - It does not primarily address the bulky lesions induced by UV light that cause exaggerated sun sensitivity. *Mismatch repair* - This system corrects errors, like **mismatched base pairs**, that are incorporated during DNA replication. - It is not directly involved in repairing DNA damage caused by environmental factors like UV radiation. *Double stranded DNA break repair* - This mechanism repairs **double-strand breaks** in DNA, which are highly deleterious lesions caused by ionizing radiation or oxidative stress. - While critical for genome stability, it is not the primary repair pathway for UV-induced DNA lesions or the direct cause of sun sensitivity.
Question 7: Which of the following is associated with defect in mismatch repair
- A. MUTYH Associated Polyposis
- B. Bloom Disorder
- C. SCID
- D. Hereditary HNPCC (Correct Answer)
Explanation: ***Hereditary HNPCC*** - **Hereditary Nonpolyposis Colorectal Cancer (HNPCC)**, also known as Lynch syndrome, is caused by inherited mutations in **DNA mismatch repair (MMR) genes** [1]. - Defective MMR leads to an accumulation of **mutations** in microsatellite regions, increasing the risk of colorectal and other cancers [1]. *MUTYH Associated Polyposis* - This condition is associated with mutations in the **MUTYH gene**, which plays a role in **base excision repair**, not mismatch repair [1]. - It leads to an increased risk of colorectal polyps and cancer, but through a different DNA repair pathway. *Bloom Disorder* - Bloom syndrome is caused by mutations in the **BLM gene**, which encodes a DNA helicase involved in **DNA replication** and repair. - It results in genomic instability, increased cancer risk, and characteristic growth retardation and photosensitivity, distinct from mismatch repair defects. *SCID* - **Severe Combined Immunodeficiency (SCID)** refers to a group of genetic disorders that impair the development and function of **T and B lymphocytes**. - While some forms involve defects in DNA repair enzymes vital for V(D)J recombination (**e.g., RAG enzymes, Artemis**), SCID is primarily an immune disorder and not directly associated with the mismatch repair pathway in the context of cancer predisposition like HNPCC. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Gastrointestinal Tract, p. 817.
Question 8: 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 9: Which is not a characteristic of Li-Fraumeni syndrome?
- A. p53 mutation
- B. Multiple primary tumors
- C. Autosomal recessive (Correct Answer)
- D. Early onset cancers
Explanation: ***Autosomal recessive*** - Li-Fraumeni syndrome is inherited in an **autosomal dominant** pattern, not autosomal recessive [1]. - This means only one copy of the altered gene in each cell is sufficient to cause the disorder. *p53 mutation* - Li-Fraumeni syndrome is directly caused by a **germline mutation** in the **TP53 tumor suppressor gene**, which codes for the p53 protein [2]. - The p53 protein normally plays a critical role in **cell cycle arrest**, DNA repair, and apoptosis, preventing tumor formation [2]. *Multiple primary tumors* - Individuals with Li-Fraumeni syndrome have a significantly increased risk of developing **multiple independent primary cancers** throughout their lifetime [1]. - These can include soft tissue sarcomas, osteosarcomas, brain tumors, adrenocortical carcinomas, and breast cancer. *Early onset cancers* - A hallmark of Li-Fraumeni syndrome is the development of **cancers at unusually young ages**, often in childhood or early adulthood. - This early onset is a key diagnostic criterion, differentiating it from sporadic cancers that typically appear later in life [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 298-300. [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.
Question 10: A patient presents with headache, confusion, and a diagnosis of a brain tumor. The family history reveals brain and kidney tumors. What is the most likely diagnosis?
- A. Neurofibromatosis
- B. Li-Fraumeni syndrome
- C. VHL syndrome (Correct Answer)
- D. Churg-Strauss syndrome
Explanation: ***VHL syndrome*** - **Von Hippel-Lindau (VHL) syndrome** is an inherited disorder characterized by the growth of tumors and cysts in various parts of the body, including the **brain (hemangioblastomas)** and **kidneys (renal cell carcinoma)**. - The presentation of a brain tumor, kidney tumors, and a positive family history for both organs strongly points to VHL syndrome. *Neurofibromatosis* - **Neurofibromatosis (NF)** typically presents with **cafe-au-lait spots**, neurofibromas, optic gliomas, and Lisch nodules. - While it involves brain tumors, kidney tumors are not a primary feature of NF. *Li-Fraumeni syndrome* - **Li-Fraumeni syndrome** is associated with an increased risk of various cancers, including **sarcomas**, **breast cancer**, **adrenocortical carcinomas**, and **leukemia**. - While brain tumors can occur, the specific combination of brain and kidney tumors with a clear family history is less characteristic of Li-Fraumeni than VHL syndrome. *Churg-Strauss syndrome* - **Churg-Strauss syndrome (Eosinophilic Granulomatosis with Polyangiitis)** is a systemic vasculitis characterized by **asthma**, **eosinophilia**, and **granulomatous inflammation**. - It does not involve the development of brain or kidney tumors.
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