Neoplasia Practice Questions

Q: The KRAS proto-oncogene is associated with which type of cancer?

Colon cancer. **Explanation:** **KRAS** (Kirsten Rat Sarcoma virus) is a proto-oncogene that encodes a small GTPase protein involved in the MAPK/ERK signaling pathway, which regulates cell growth and survival. When mutated, the KRAS protein remains constitutively active (locked in the GTP-bound state), leading to uncontrolled cellular proliferation. **Why Colon Cancer is Correct:** KRAS mutations are a hallmark of the **adenoma-carcinoma sequence** in colorectal cancer. They occur in approximately 40-50% of colorectal cancers, typically representing the transition from a small adenoma to a larger, more dysplastic polyp. Clinically, KRAS mutation status is a critical biomarker; tumors harboring these mutations are resistant to anti-EGFR biological therapies like **Cetuximab** and **Panitumumab**. **Analysis of Incorrect Options:** * **Breast Cancer:** Primarily associated with mutations in **BRCA1/BRCA2** (tumor suppressors) or amplification of **HER2/neu** (ERBB2). * **Bladder Cancer:** Most commonly associated with mutations in **FGFR3** or **HRAS** (specifically in low-grade papillary variants) and **TP53/RB** in high-grade invasive types. * **Melanoma:** Strongly associated with mutations in the **BRAF** gene (specifically the V600E mutation) and **NRAS**, rather than KRAS. **High-Yield Clinical Pearls for NEET-PG:** * **RAS Family:** KRAS (Colon, Lung, Pancreas), HRAS (Bladder, Kidney), NRAS (Melanoma, Hematologic malignancies). * **Pancreatic Cancer:** KRAS is the most frequently mutated oncogene here (>90% of cases) [1]. * **Mechanism:** RAS proteins have intrinsic GTPase activity which is impaired in mutations, preventing the hydrolysis of GTP to GDP. * **GAPs (GTPase Activating Proteins):** These act as "brakes" on RAS; loss of GAPs (like Neurofibromin 1 in NF1) leads to prolonged RAS activation. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Pancreas, pp. 897-898.

Q: The tumor suppressor gene p53 induces cell cycle arrest at which phase?

G1-S phase. **Explanation:** The **p53 protein**, often referred to as the "Guardian of the Genome," is a critical tumor suppressor gene located on chromosome 17p. Its primary function is to maintain genomic stability by monitoring DNA damage. **Why G1-S is correct:** When DNA damage is detected, p53 levels rise and act as a transcription factor for **p21** (a Cyclin-Dependent Kinase Inhibitor). p21 inhibits the **Cyclin D/CDK4** and **Cyclin E/CDK2** complexes. These complexes are responsible for phosphorylating the Retinoblastoma (Rb) protein. By keeping Rb in its hypophosphorylated (active) state, it remains bound to the E2F transcription factor, preventing the cell from transitioning from the **G1 phase to the S phase** [1]. This arrest allows time for DNA repair; if repair fails, p53 induces apoptosis via the BAX/BCL-2 pathway. **Analysis of Incorrect Options:** * **G2-M phase:** While p53 can play a minor role here, the primary regulator of the G2-M checkpoint is the inhibition of the Cdc25 phosphatase and the Cyclin B/CDK1 complex. * **S-G2 phase:** This is not a primary regulatory checkpoint for p53-mediated cell cycle arrest. * **G0 phase:** This is a quiescent, non-dividing state. p53 acts on actively cycling cells to prevent them from replicating damaged DNA, rather than inducing a transition into G0. **High-Yield Clinical Pearls for NEET-PG:** * **Li-Fraumeni Syndrome:** A germline mutation in the *TP53* gene leading to multiple early-onset cancers (SBLA syndrome: Sarcoma, Breast, Leukemia, Adrenal gland). * **Most Common Mutation:** *TP53* is the most frequently mutated gene in human cancers. * **HPV Association:** Human Papillomavirus (HPV) E6 protein degrades p53, while E7 inhibits Rb, leading to cervical cancer.

Question 1

Carcinogenesis of benzopyrene in animals occurs due to all of the following mechanisms except:

Accepted Answer

Cytochrome P450 activation

Answer

Epoxide formation

Answer

p53 activation

Answer

Induction of metabolism by Cytochrome P450

Question 2

The cell with an increased mitotic rate that resembles the undifferentiated mesenchymal cells of the same origin is:

Accepted Answer

Anaplastic

Answer

Dysplastic

Answer

Metaplastic

Answer

Hyperplastic

Question 3

Which of the following is a wrong association?

Accepted Answer

Cytomegalovirus (CMV) - Nasopharyngeal Carcinoma

Answer

Human Papillomavirus (HPV) - Cervical Carcinoma (CaCx)

Answer

Epstein-Barr Virus (EBV) - Burkitt's Lymphoma

Answer

Human Herpesvirus 8 (HHV-8) - Kaposi Sarcoma

Question 4

The KRAS proto-oncogene is associated with which type of cancer?

Accepted Answer

Colon cancer

Answer

Breast cancer

Answer

Bladder cancer

Answer

Melanoma

Question 5

The tumor suppressor gene p53 induces cell cycle arrest at which phase?

Accepted Answer

G1-S phase

Answer

G2-M phase

Answer

S-G2 phase

Answer

G0 phase

Question 6

Spindle cell carcinoma is a variant of which type of carcinoma?

Accepted Answer

Squamous cell carcinoma

Answer

Pleomorphic adenoma

Answer

Adenoid cystic carcinoma

Answer

Basal cell carcinoma

Question 7

Loss of heterozygosity is associated with which of the following conditions?

Accepted Answer

Retinoblastoma

Answer

Acute myeloid leukemia

Answer

Acute lymphoblastic leukemia

Answer

Acute promyelocytic leukemia

Question 8

Which condition is associated with the S-100 marker?

Accepted Answer

Malignant melanoma

Answer

Multiple myeloma

Answer

Prostate carcinoma

Answer

Medullary carcinoma thyroid

Question 9

Smoking is a causative factor for all the following carcinomas, except:

Accepted Answer

Nasopharyngeal carcinoma

Answer

Esophageal carcinoma

Answer

Laryngeal carcinoma

Answer

Urinary bladder carcinoma

Question 10

All of the following statements are true about tumor suppressor gene TP53, except?

Accepted Answer

Activity in the cells decreases following UV irradiation and stimulates cell cycle.

Answer

Regulates genes involved in cell cycle regulation.

Answer

Increased levels can induce apoptosis.

Answer

Inherited TP53 mutations give rise to Li-Fraumeni syndrome.

Neoplasia — MCQs

Neoplasia — MCQs

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