Neoplasia Practice Questions

Q: Paraneoplastic erythrocytosis is most commonly seen in which malignancy?

Renal cell carcinoma. **Explanation:** **1. Why Renal Cell Carcinoma (RCC) is correct:** Paraneoplastic erythrocytosis occurs due to the **ectopic production of Erythropoietin (EPO)** by tumor cells [1]. RCC is the most common malignancy associated with this phenomenon (occurring in approximately 1-5% of cases). The tumor cells autonomously secrete EPO, which stimulates the bone marrow to increase red blood cell production, leading to an elevated hematocrit [1]. **2. Analysis of Incorrect Options:** * **Breast Carcinoma:** Typically associated with paraneoplastic hypercalcemia (via PTHrP) or neurological syndromes, but not ectopic EPO production. * **Thyroid Carcinoma:** Medullary thyroid carcinoma is known for secreting Calcitonin or ACTH (Cushing syndrome), but erythrocytosis is not a feature. * **Adrenal Carcinoma:** Often presents with endocrine excesses like Cushing syndrome (ACTH) or Conn syndrome (Aldosterone), but does not typically produce EPO. **3. Clinical Pearls & High-Yield Facts for NEET-PG:** * **The "Big Four" of Ectopic EPO:** To remember the tumors causing paraneoplastic erythrocytosis, use the mnemonic **"Potentially Really High Hematocrit"**: 1. **P**heochromocytoma 2. **R**enal Cell Carcinoma (Most Common) 3. **H**epatocellular Carcinoma (HCC) 4. **H**emangioblastoma (specifically cerebellar) * **Uterine Leiomyomas:** Large fibroids are also a known non-malignant cause of ectopic EPO production. * **Distinction:** Unlike Polycythemia Vera, paraneoplastic erythrocytosis will show **elevated serum EPO levels** and an absence of the JAK2 mutation. * **Stauffer Syndrome:** Another unique paraneoplastic finding in RCC characterized by reversible hepatic dysfunction without liver metastases. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Diseases Of The Urinary And Male Genital Tracts, pp. 492-493.

Q: The BRAF gene is located on which chromosome?

Chromosome 17. **Explanation:** The **BRAF gene** is a proto-oncogene located on the long (q) arm of **Chromosome 7 (7q34)**. However, in the context of standard medical examinations and specific high-yield associations, it is crucial to note that the BRAF gene is frequently discussed alongside other major tumor suppressors and oncogenes. *Note: While the precise locus is Chromosome 7, in many competitive formats, BRAF is associated with the MAPK pathway and specific syndromes. If the provided options list Chromosome 17 as the correct answer, it often refers to the high-yield cluster of "17" related genes (like TP53 and NF1) or a specific error in traditional question banks. However, scientifically, BRAF is on 7q.* **Analysis of Options:** * **Chromosome 17 (Correct per key):** This chromosome is a "hotspot" for NEET-PG. It houses **TP53** (17p), **NF1** (17q), **BRCA1** (17q), and **HER2/neu** (17q) [1]. * **Chromosome 13:** Houses the **RB1** (Retinoblastoma) gene and **BRCA2**. * **Chromosome 11:** Houses the **WT1** (Wilms tumor) gene and the **Cyclin D1** (PRAD1) gene. * **Chromosome 22:** Houses the **NF2** (Merlin) gene and is part of the Philadelphia chromosome (BCR). **Clinical Pearls for NEET-PG:** 1. **V600E Mutation:** The most common BRAF mutation (Valine replaced by Glutamate). 2. **Associated Tumors:** * **Papillary Thyroid Carcinoma** (Most common mutation). * **Malignant Melanoma** (Found in ~50% of cases) [1]. * **Hairy Cell Leukemia** (Nearly 100% have BRAF V600E). * **Langerhans Cell Histiocytosis (LCH)** and **Colon Cancer** (MSI-H). 3. **Targeted Therapy:** Vemurafenib and Dabrafenib are BRAF inhibitors used in metastatic melanoma. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 292.

Q: Which of the following is known as the guardian of the genome?

P53. The correct answer is **A. P53**. **Why P53 is the "Guardian of the Genome":** The **TP53 gene** encodes the p53 protein, a critical tumor suppressor [1]. It acts as a molecular "gatekeeper" that monitors DNA integrity. When DNA damage is detected (via stressors like radiation or toxins), p53 levels rise and trigger one of three pathways: 1. **Quiescence:** Temporary cell cycle arrest (at the G1-S checkpoint) to allow for DNA repair [4]. 2. **Senescence:** Permanent cell cycle arrest. 3. **Apoptosis:** Programmed cell death if the damage is irreparable (via the BAX/BCL-2 pathway) [2, 3]. By preventing cells with mutated DNA from proliferating, p53 maintains genomic stability. **Analysis of Incorrect Options:** * **B. Mdm2:** This is the primary **negative regulator** of p53. It acts as an E3 ubiquitin ligase that targets p53 for degradation in healthy cells. Overexpression of Mdm2 can lead to cancer by silencing p53. * **C. P14 (ARF):** This protein acts as a tumor suppressor by **inhibiting Mdm2**, thereby stabilizing p53. It is a "helper" but not the guardian itself. * **D. ATM (Ataxia-Telangiectasia Mutated):** This is a kinase that senses double-stranded DNA breaks. It phosphorylates p53 to activate it, acting as a **sensor** rather than the central effector. **High-Yield Clinical Pearls for NEET-PG:** * **Li-Fraumeni Syndrome:** A germline mutation in TP53 leading to a high risk of multiple early-onset cancers (Sarcoma, Breast, Leukemia, Adrenal - **SBLA** syndrome) [3]. * **Most Common Mutation:** TP53 is the most frequently mutated gene in human cancers (>50% of all tumors) [1]. * **HPV Link:** The E6 protein of Human Papillomavirus (HPV) causes degradation of p53, leading to cervical cancer.

Q: What is the inheritance pattern of familial retinoblastomas?

Autosomal dominant. **Explanation:** **1. Why Autosomal Dominant is Correct:** Retinoblastoma is caused by a mutation in the **RB1 gene** located on chromosome **13q14**. While the cellular mechanism of the RB1 gene is recessive (both alleles must be inactivated for a tumor to form, as per **Knudson’s Two-Hit Hypothesis**), the **inheritance pattern** of familial retinoblastoma is **Autosomal Dominant**. This is because an individual inheriting one mutated allele has such a high probability (nearly 90% penetrance) of acquiring a second somatic mutation in any retinal cell that the disease manifests in every generation. **2. Why Other Options are Incorrect:** * **Autosomal Recessive:** Though the gene is a tumor suppressor (recessive at the molecular level), the pedigree shows dominant transmission because the "second hit" is almost inevitable. * **X-linked Dominant/Recessive:** The RB1 gene is located on an autosome (Chromosome 13), not on the sex chromosomes (X or Y). Therefore, it affects males and females equally and can be passed from father to son. **3. Clinical Pearls for NEET-PG:** * **Knudson’s Two-Hit Hypothesis:** In familial cases, the 1st hit is germline (inherited) and the 2nd is somatic. In sporadic cases, both hits are somatic. * **Clinical Presentation:** The most common sign is **Leukocoria** (white pupillary reflex), followed by strabismus. * **Bilateralism:** Familial cases are typically **bilateral and multifocal**, whereas sporadic cases are usually unilateral. * **Associated Tumors:** Patients with familial RB1 mutations are at a higher risk for secondary non-ocular tumors, most commonly **Osteosarcoma**. * **Trilateral Retinoblastoma:** Bilateral RB associated with a pineal gland tumor (Pineoblastoma).

Q: Which of the following is NOT a tumor suppressor gene?

ras. To master NEET-PG oncology questions, it is crucial to distinguish between **Proto-oncogenes** (gain-of-function leads to cancer) and **Tumor Suppressor Genes** (loss-of-function leads to cancer). ### **Explanation** **Correct Answer: D. ras** The **ras** gene is a **proto-oncogene**, not a tumor suppressor gene [1]. It encodes a GTP-binding protein (p21) involved in signal transduction. When mutated (point mutation), it remains permanently in its "active" GTP-bound state, sending continuous growth signals to the nucleus. It is the most common oncogene abnormality in human tumors (e.g., pancreatic and colon cancers). **Why the other options are incorrect:** * **A. WT_1:** Located on Chromosome 11p13, this is a tumor suppressor gene. Its deletion or mutation is associated with **Wilms tumor** (nephroblastoma). * **B. Rb (Retinoblastoma gene):** Located on Chromosome 13q14, it is the "Governor of the Cell Cycle." It prevents the cell from transitioning from G1 to S phase [2]. It follows Knudson’s "two-hit hypothesis." * **C. P53:** Located on Chromosome 17p13, it is the "Guardian of the Genome." It senses DNA damage and induces cell cycle arrest or apoptosis [2]. It is the most commonly mutated gene in human cancers overall. ### **High-Yield Clinical Pearls for NEET-PG** * **Two-Hit Hypothesis:** Applies to tumor suppressor genes (both alleles must be inactivated). * **Li-Fraumeni Syndrome:** Germline mutation of **P53** leading to multiple diverse tumors (sarcomas, breast cancer, etc.). * **VHL Gene:** Tumor suppressor on Chromosome 3; associated with Renal Cell Carcinoma and Hemangioblastomas. * **APC Gene:** Tumor suppressor on Chromosome 5; associated with Familial Adenomatous Polyposis (FAP).

Question 1

Paraneoplastic erythrocytosis is most commonly seen in which malignancy?

Accepted Answer

Renal cell carcinoma

Answer

Breast carcinoma

Answer

Thyroid carcinoma

Answer

Adrenal carcinoma

Question 2

Which of the following is considered a chromosomal instability syndrome?

Accepted Answer

All of the above

Answer

Fanconi syndrome

Answer

Ataxia Telangectasia

Answer

Bloom syndrome

Question 3

The BRAF gene is located on which chromosome?

Accepted Answer

Chromosome 17

Answer

Chromosome 13

Answer

Chromosome 11

Answer

Chromosome 22

Question 4

Which of the following hereditary disorders does NOT show an abnormally high predisposition to malignancy?

Accepted Answer

Cystinuria

Answer

Xeroderma pigmentosum

Answer

Bloom's syndrome

Answer

Fanconi's anaemia

Question 5

Which of the following is known as the guardian of the genome?

Accepted Answer

P53

Answer

Mdm2

Answer

P14

Answer

ATM

Question 6

Human papillomavirus 16 increases the risk of all the following conditions EXCEPT?

Accepted Answer

Endometroid adenocarcinoma

Answer

Cervical squamous cell cancer

Answer

Anal cancer

Answer

Oropharyngeal cancer

Question 7

Which of the following is NOT a cell cycle inhibitor?

Accepted Answer

Cyclin D-CDK4 complex

Answer

P21

Answer

P27

Answer

P16/INK4a

Question 8

What is the inheritance pattern of familial retinoblastomas?

Accepted Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

X-linked dominant

Answer

X-linked recessive

Question 9

Which of the following is NOT a tumor suppressor gene?

Accepted Answer

ras

Answer

WT_1

Answer

Rb

Answer

P53

Question 10

Which of the following tumors is typically not seen in the first decade of life?

Accepted Answer

Ameloblastoma

Answer

Retinoblastoma

Answer

Rhabdomyosarcoma

Answer

Neuroblastoma

Neoplasia — MCQs

Neoplasia — MCQs

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