Molecular Pathology Practice Questions

Q: What is the primary pathology in Zellweger syndrome?

Peroxisomal defect. **Explanation:** **Zellweger Syndrome** (also known as cerebrohepatorenal syndrome) is the most severe form of the **Peroxisome Biogenesis Disorders (PBD)**. It is an autosomal recessive condition caused by mutations in the **PEX genes**, which are essential for the normal assembly and functioning of peroxisomes. 1. **Why Option C is Correct:** Peroxisomes are organelles responsible for the beta-oxidation of **Very Long Chain Fatty Acids (VLCFA)** and the synthesis of plasmalogens (vital for myelin). In Zellweger syndrome, the failure to import proteins into the peroxisome leads to "empty" peroxisomes. This results in the systemic accumulation of VLCFAs, particularly in the brain and liver, leading to severe neurological dysfunction and organ failure. 2. **Why Other Options are Incorrect:** * **Option A (Mitochondrial defect):** While mitochondria also perform fatty acid oxidation, they handle short, medium, and long-chain fatty acids. Mitochondrial diseases typically present with myopathy, lactic acidosis, and "ragged red fibers," which are distinct from the peroxisomal pathology of Zellweger. * **Option B (Glycoxisomal defect):** Glyoxysomes are specialized peroxisomes found in plants (involved in the glyoxylate cycle); they do not exist in human pathology. **High-Yield Clinical Pearls for NEET-PG:** * **Clinical Triad:** Dysmorphic craniofacial features (high forehead, wide fontanelles), severe hypotonia ("floppy baby"), and neonatal seizures. * **Imaging/Pathology:** Look for **chondrodysplasia punctata** (stippled epiphyses on X-ray) and renal cortical cysts. * **Biochemical Marker:** Elevated serum levels of **Very Long Chain Fatty Acids (VLCFA)** is the diagnostic hallmark. * **Prognosis:** Usually fatal within the first year of life.

Q: AKT1 E17K somatic mutation is associated with which of the following carcinomas?

Breast carcinoma. **Explanation:** The **AKT1 E17K** mutation is a specific somatic point mutation occurring in the pleckstrin homology domain of the AKT1 protein. This mutation results in the constitutive localization of AKT1 to the plasma membrane, leading to the permanent activation of the **PI3K/AKT/mTOR pathway**, which promotes cell survival, growth, and proliferation. **1. Why Breast Carcinoma is correct:** The AKT1 E17K mutation is most frequently identified in **Breast Carcinoma**, specifically in **Estrogen Receptor-positive (ER+)** and **ductal** subtypes. It occurs in approximately 2–5% of breast cancers. It is often mutually exclusive with PIK3CA mutations, suggesting they serve redundant roles in activating the same oncogenic pathway. **2. Analysis of Incorrect Options:** * **Gastric Carcinoma:** While the PI3K pathway is often altered in gastric cancer, it is usually via *PIK3CA* mutations or *PTEN* loss, rather than the specific AKT1 E17K mutation. * **Ovarian Carcinoma:** AKT2 amplification is more common in ovarian cancer. AKT1 mutations are rare in this site. * **Pancreatic Carcinoma:** The hallmark mutation in pancreatic cancer is *KRAS* (found in >90% of cases), not AKT1. **High-Yield Clinical Pearls for NEET-PG:** * **AKT1 E17K** is a "gain-of-function" mutation. * **PI3K/AKT/mTOR Pathway:** This is a major target for newer "targeted therapies" (e.g., Alpelisib for PIK3CA). * **Mutual Exclusivity:** In breast cancer, AKT1 mutations, PIK3CA mutations, and PTEN loss rarely occur in the same tumor. * **Other associations:** Besides breast cancer, AKT1 E17K is also notably found in **Proteus Syndrome** (a mosaic genetic disorder) and some cases of endometrial cancer.

Q: The NF-2 gene codes for which protein?

Merlin. The **NF-2 gene**, located on **chromosome 22q12**, is a tumor suppressor gene. It encodes a protein called **Merlin** (also known as Schwannomin). Merlin is structurally related to the ERM (Ezrin-Radixin-Moesin) family of proteins. Its primary function is to link cell-surface glycoproteins to the actin cytoskeleton. When Merlin is lost, cells lose contact inhibition, leading to uncontrolled proliferation and tumor formation. [1] **Analysis of Options:** * **Option C (Merlin):** Correct. Merlin acts as a tumor suppressor by facilitating contact inhibition through the Hippo signaling pathway. [1] * **Option B (Neurofibromin):** Incorrect. This protein is encoded by the **NF-1 gene** located on chromosome 17. Neurofibromin acts as a GTPase-activating protein (GAP) that downregulates the RAS signaling pathway. [1] * **Options A & D (Catenins):** Incorrect. Catenins (α and β) are proteins that interact with E-cadherin to maintain cell-cell adhesion. While β-catenin is involved in the WNT signaling pathway (mutated in APC/Colon cancer), it is not the product of the NF-2 gene. **High-Yield Clinical Pearls for NEET-PG:** * **Clinical Presentation:** NF-2 is classically associated with **Bilateral Acoustic Neuromas** (Vestibular Schwannomas). Remember the mnemonic: **NF-2** = **2** ears (Bilateral acoustic neuromas) on chromosome **22**. [1] * **MISME Syndrome:** NF-2 is characterized by **M**ultiple **I**nherited **S**chwannomas, **M**eningiomas, and **E**pendymomas. [2] * **Ocular Sign:** Juvenile posterior subcapsular lenticular opacities (cataracts) are a common early diagnostic sign of NF-2. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1248-1249. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1319-1320.

Question 1

What is the primary pathology in Zellweger syndrome?

Accepted Answer

Peroxisomal defect

Answer

Mitochondrial defect

Answer

Glycoxisomal defect

Answer

None of the above

Question 2

AKT1 E17K somatic mutation is associated with which of the following carcinomas?

Accepted Answer

Breast carcinoma

Answer

Gastric carcinoma

Answer

Ovarian carcinoma

Answer

Pancreatic carcinoma

Question 3

Ladder pattern of DNA electrophoresis is seen in which of the following cellular processes?

Accepted Answer

Apoptosis

Answer

Necrosis

Answer

Cytolysis

Answer

Karyorrhexis

Question 4

Cellular adaptation maintained even after partial liver resection is known as:

Accepted Answer

Hyperplasia

Answer

Hypertrophy

Answer

Metaplasia

Answer

Dysplasia

Question 5

Fat necrosis is seen in which organ?

Accepted Answer

Breast

Answer

Brain

Answer

Kidney

Answer

Spleen

Question 6

Which of the following is NOT true about chromosomal instability syndromes?

Accepted Answer

Autosomal dominant inheritance

Answer

DNA repair defect

Answer

Increased risk of malignancy

Answer

Associated immunodeficiency

Question 7

The NF-2 gene codes for which protein?

Accepted Answer

Merlin

Answer

α Catenin

Answer

Neurofibromin

Answer

α β Catenin

Question 8

A female patient presented with a firm mass of 2 x 2 cms in the upper outer quadrant of the breast. She gives a family history of ovarian carcinoma. Which investigation needs to be done to assess for a relevant mutation?

Accepted Answer

BRCA-2

Answer

p53

Answer

Her 2/Neu gene

Answer

C-myc gene

Question 9

Tumor necrosis factor (TNF) is secreted by activated:

Accepted Answer

Macrophages

Answer

Neutrophils

Answer

Lymphocytes

Answer

Eosinophils

Question 10

Which of the following represents the indication for the In-situ DNA nick end labeling technique?

Accepted Answer

To detect the fraction of cells in apoptotic pathways

Answer

To detect the fraction of cells in S phase

Answer

To detect p53 gene product

Answer

To detect bcr/abl gene

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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