Molecular Pathology — MCQs

Molecular Pathology Indian Medical PG Practice Questions and MCQs

Question 241: Gene instability associated with malignancy is seen in which of the following conditions?

A. Ataxia telangiectasia (Correct Answer)
B. Marfan's syndrome
C. Sickle cell disease
D. Klippel-Feil syndrome

Explanation: ***Ataxia telangiectasia*** - Characterized by **mutation in the ATM gene**, leading to impaired DNA repair and increased genomic instability [1], which is closely associated with malignancies like lymphomas and leukemias [1]. - Patients often present with **telangiectasia**, ataxia [2], and increased sensitivity to radiation due to this DNA repair defect. *Sickle cell disease* - A genetic disorder caused by a mutation in the **HBB gene**, leading to deformed red blood cells, not primarily linked to **gene instability**. - Its complications include **vaso-occlusive crises** and organ damage rather than malignancy. *Marfan's syndrome* - Caused by mutations in the **FBN1 gene**, it primarily affects connective tissue and has no direct association with gene instability or malignancy. - Clinical features include **tall stature**, **long limbs**, and cardiovascular issues like aortic dilation, but not increased cancer risk. *Klippel field syndrome* - This is a vascular disorder characterized by **arteriovenous malformations**, and it does not relate to gene instability or increased cancer susceptibility. - Symptoms are primarily related to **vascular anomalies** impacting the skin and underlying structures, not a predisposition for malignancy. **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. 212-213, 225-227. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1300-1301.

Question 242: What is the target gene that is affected by the E6 gene product of HPV, leading to malignant transformation?

A. C-myc gene (proto-oncogene)
B. N-myc gene (proto-oncogene)
C. p53 gene (tumor suppressor gene) (Correct Answer)
D. RAS gene (involved in signaling)

Explanation: ***p53 gene (tumor suppressor gene)*** - The **E6 gene product of HPV** inactivates the **p53 tumor suppressor protein**, which normally functions to halt cell growth or induce apoptosis in response to DNA damage [1], [2]. - Degradation of p53 by E6 leads to **uncontrolled cell proliferation** and genomic instability, contributing significantly to malignant transformation [1]. *C-myc gene (proto-oncogene)* - While **c-myc** is a proto-oncogene involved in cell growth and proliferation, it is not the primary target directly affected by the HPV E6 protein. - Activation of c-myc can be a secondary event in carcinogenesis, but it's not the direct mechanism by which E6 promotes malignancy. *N-myc gene (proto-oncogene)* - **N-myc** is another proto-oncogene, often associated with neuroblastoma, and is not a direct target of the HPV E6 oncoprotein. - Its role in HPV-induced cancers is not central to the mechanism of E6. *RAS gene (involved in signaling)* - The **RAS gene** is a proto-oncogene encoding proteins involved in cell signaling pathways that regulate cell growth and differentiation [2]. - Mutations in RAS are common in various cancers, but the HPV E6 protein does not primarily target or inactivate the RAS gene or its protein products for malignant transformation. **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. 301-304.

Question 243: Best sample for karyotyping is?

A. Blood (Correct Answer)
B. Bone marrow
C. Amniotic fluid
D. Chorionic villi

Explanation: ***Blood*** - **Peripheral blood lymphocytes** are easily accessible and stimulate to divide in culture, providing sufficient metaphase cells for karyotyping. - This is the most common and least invasive method for routine **karyotyping** in adults and children. *Bone marrow* - While bone marrow cells can be used for karyotyping, especially in diagnosing **hematological malignancies**, it is a more invasive procedure than a blood draw [1]. - Bone marrow is primarily used when there is suspicion of a **chromosomal abnormality** specifically affecting hematopoietic cells, such as in leukemia [1]. *Amniotic fluid* - **Amniotic fluid** is collected via **amniocentesis** and contains fetal cells, making it suitable for prenatal karyotyping. - However, it is an **invasive procedure** reserved for specific prenatal diagnostic indications, not routine karyotyping in postnatal individuals. *Chorionic villi* - **Chorionic villi** are obtained via **chorionic villus sampling (CVS)** and provide fetal cells for early prenatal karyotyping. - Like amniotic fluid, CVS is an **invasive prenatal diagnostic** test and not the "best" or most common sample for general karyotyping. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 584-585.

Question 244: Which of the following methods is commonly used to study oncogenes?

A. Transformation (Correct Answer)
B. Transduction
C. Conjugation
D. Gene editing (e.g., CRISPR)

Explanation: ***Transformation*** - **Transformation** is the classical and most commonly used method to study oncogenes in the laboratory. - In this technique, **oncogenes are introduced into normal cells** (often NIH 3T3 fibroblasts) to observe whether they can induce **malignant transformation** [1]. - Transformed cells exhibit characteristic changes including **loss of contact inhibition**, **anchorage-independent growth** (colony formation in soft agar), **immortalization**, and ability to form tumors in nude mice. - This method has been fundamental in **identifying and characterizing oncogenes** since the 1970s and remains a gold standard for functional oncogene studies [1]. *Transduction* - **Transduction** involves introducing oncogenes into cells using **viral vectors** (especially retroviruses) [1]. - While this is indeed a common method for delivering oncogenes in research, it is a **technique for gene delivery** rather than the broader experimental approach. - Often used in conjunction with transformation assays. *Conjugation* - **Conjugation** is a mechanism of horizontal gene transfer in **bacteria** involving direct cell-to-cell contact. - This is **not relevant** for studying oncogenes in mammalian/eukaryotic cells where cancer biology is studied. *Gene editing (e.g., CRISPR)* - **CRISPR** and other gene editing technologies are modern tools that allow precise manipulation of endogenous genes. - While increasingly used in oncogene research, CRISPR is a **newer technique** and not the **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. 228-230.

Question 245: Which of the following genes is least likely to be involved in the development of carcinoma of the colon?

A. K-ras
B. Beta-Catenin (Correct Answer)
C. APC
D. Mismatch Repair Genes

Explanation: ***Beta-Catenin*** - While **beta-catenin protein accumulation** is critical in colorectal cancer pathogenesis (primarily through APC mutations), direct mutations in the **CTNNB1 gene** (encoding beta-catenin) are **rare in colorectal cancer** (~5% of cases) [1]. - Most colorectal cancers achieve beta-catenin activation indirectly through **APC inactivation**, making beta-catenin gene mutations the least likely mechanism among the listed options [1]. - This contrasts with other cancers (e.g., hepatocellular carcinoma, endometrial cancer) where direct CTNNB1 mutations are more common. *APC* - The **adenomatous polyposis coli (APC) gene** is mutated in approximately **80% of sporadic colorectal cancers**, representing the earliest and most common genetic alteration in the **adenoma-carcinoma sequence** [1]. - APC loss leads to beta-catenin accumulation and constitutive **Wnt pathway activation**, driving uncontrolled cell proliferation [2]. - Germline APC mutations cause **familial adenomatous polyposis (FAP)** [5]. *K-ras* - **K-ras oncogene** mutations occur in **30-50% of colorectal cancers**, typically as an intermediate event in the adenoma-carcinoma progression [1]. - These activating mutations lead to constitutive signaling through the **MAPK pathway**, promoting cell proliferation and survival independent of growth factor signals. *Mismatch Repair Genes* - **Mismatch repair (MMR) genes** (MLH1, MSH2, MSH6, PMS2) are involved in **15-20% of all colorectal cancers** [4]. - Germline mutations cause **Lynch syndrome (HNPCC)** (~3% of CRCs) [5]. - Sporadic **MLH1 promoter hypermethylation** accounts for 12-15% of colorectal cancers, leading to **microsatellite instability (MSI-high)** tumors [3]. - MMR deficiency represents an alternative, well-established pathway of colorectal carcinogenesis. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Gastrointestinal Tract, p. 819. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 304-305. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Gastrointestinal Tract, pp. 819-821. [4] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Alimentary System Disease, pp. 373-374. [5] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Gastrointestinal Tract, pp. 821-822.

Question 246: The gene most commonly involved in endometrial carcinoma is:

A. PTEN (Correct Answer)
B. BRAF
C. KRAS
D. Mismatch repair genes

Explanation: ***PTEN*** - **PTEN** (phosphatase and tensin homolog) is a **tumor suppressor gene** frequently inactivated in **endometrial carcinoma**, particularly in cases of **endometrioid histology**. - Loss of PTEN function leads to uncontrolled cell proliferation and survival by activating the **PI3K/Akt signaling pathway**, contributing to tumor development. *BRAF* - **BRAF mutations** are most commonly associated with **melanoma** and certain types of **thyroid cancer**, specifically papillary thyroid carcinoma. - While BRAF mutations can be found in a small subset of other cancers, they are not a primary driver or common gene in endometrial carcinoma. *KRAS* - **KRAS mutations** are frequently observed in **colorectal cancer**, **pancreatic cancer**, and **non-small cell lung cancer**. - Though KRAS can be mutated in various cancers, it is not the most commonly involved gene in endometrial carcinoma. *Mismatch repair genes* - Mutations in **mismatch repair (MMR) genes** (e.g., MLH1, MSH2, MSH6, PMS2) are characteristic of **Lynch syndrome** and lead to **microsatellite instability (MSI)**. - While MSI is observed in a significant subset of endometrial cancers (especially those associated with Lynch syndrome), PTEN mutations are more broadly common across all types of endometrial carcinoma.

Question 247: Which genetic mutation is most commonly associated with male breast carcinoma?

A. BRCA2 mutation (Correct Answer)
B. TP53 mutation
C. PALB2 mutation
D. BRCA1 mutation

Explanation: ***BRCA2 mutation*** - **BRCA2 mutations** are the most common genetic mutations found in men with **breast cancer**, significantly increasing their lifetime risk. - They are also associated with an increased risk of **prostate cancer**, **pancreatic cancer**, and **melanoma** in men. *TP53 mutation* - **TP53 mutations** are associated with **Li-Fraumeni syndrome**, a hereditary cancer syndrome that increases the risk of various cancers, including sarcomas, brain tumors, and early-onset breast cancer in women. - While it can increase breast cancer risk, it is less commonly associated with **male breast carcinoma** compared to BRCA2. *PALB2 mutation* - **PALB2 (Partner And Localizer of BRCA2) mutations** are associated with an increased risk of breast cancer in both men and women, acting in concert with BRCA2. - While impactful, they are less prevalent than **BRCA2 mutations** in male breast cancer overall. *BRCA1 mutation* - **BRCA1 mutations** primarily increase the risk of breast and ovarian cancer in women. While they can increase the risk of **male breast cancer** to some extent, their contribution is much lower than that of **BRCA2 mutations** [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, pp. 1058-1059.

Question 248: The given karyotype is seen in which of the following syndromes?

A. Angelman syndrome
B. Fragile x syndrome
C. Down syndrome (Correct Answer)
D. Turner syndrome

Explanation: ***Correct: Down syndrome*** - The karyotype shows **trisomy 21** (47 chromosomes with an extra chromosome 21), which causes **Down syndrome**. - This is the most common chromosomal abnormality, with characteristic karyotype showing **three copies of chromosome 21**. - Clinical features include intellectual disability, characteristic facies, and congenital heart defects. *Incorrect: Angelman syndrome* - Caused by **deletion or mutation of UBE3A gene** on chromosome 15, not trisomy 21. - Shows normal chromosomal number (46 chromosomes), unlike the **47 chromosomes** seen in this karyotype. - Characterized by developmental delay, seizures, and happy demeanor. *Incorrect: Fragile X syndrome* - Results from **CGG repeat expansion** in the FMR1 gene on the X chromosome. - Typically shows **normal karyotype structure** (46 chromosomes), not the **extra chromosome 21** visible here. - Most common inherited cause of intellectual disability. *Incorrect: Cri du chat syndrome* - Caused by **deletion on chromosome 5p**, which would show as a **missing chromosomal segment**. - The karyotype would show **46 chromosomes with 5p deletion**, not **47 chromosomes with trisomy 21**. - Named for characteristic cat-like cry in infancy. *Incorrect: Turner syndrome* - Results from **missing X chromosome** (45,X karyotype) in females. - Shows **45 chromosomes total**, not the **47 chromosomes with extra chromosome 21** seen here. - Presents with short stature and ovarian dysgenesis.

Question 249: In breast cancer, Her-2/Neu promotes tumorigenesis by what mechanism?

A. Overexpression (Correct Answer)
B. Suppression
C. Mutation
D. Translocation

Explanation: ***Promoting cell proliferation through overexpression*** - Overexpression of Her-2/Neu leads to increased **cell proliferation**, a key feature in the progression of breast cancer [1,2]. - It is often associated with **aggressive tumor behavior** and poorer prognosis in patients [1]. *Alteration in gene expression* - While Her-2/Neu may influence gene expression, it primarily functions through **signaling pathways** that promote cell division rather than through alteration itself. - This oes not directly correlate with the specific impact of Her-2/Neu in tumor progression. *Gene amplification* - Gene amplification refers to the increased number of copies of the Her-2 gene, but does not directly describe its role in empowered **proliferation** or tumor advancement [1,3]. - This process is a mechanism but doesn't explain how it promotes cancer progression effectively. *Inhibiting tumor growth* - Her-2/Neu does not inhibit tumor growth; rather, it is **associated with aggressive growth** and poor prognosis in breast cancer [1]. - This ontradicts the established role of Her-2/Neu in promoting cancer rather than suppressing it. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, p. 1066. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, pp. 1059-1060. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 292.

Question 250: Which of the following is not a chromosome breakage disorder?

A. Bloom syndrome
B. Ataxia telangiectasia
C. Duchenne muscular dystrophy (Correct Answer)
D. Fanconi anemia

Explanation: ***Duchenne muscular dystrophy*** - Duchenne muscular dystrophy is primarily a **muscle degeneration disorder** caused by mutations in the **dystrophin gene**, not a chromosome breakage disorder. - It does not involve issues with **chromosomal stability** or breakage, unlike the others listed. *Ataxia telangiectasia* - Ataxia telangiectasia is associated with defects in **DNA repair mechanisms**, leading to **chromosome breakage** and instability [1]. - Patients exhibit progressive **ataxia**, **telangiectasia**, and increased sensitivity to radiation. *Fanconi anemia* - Fanconi anemia is characterized by a defect in the **DNA repair pathway**, resulting in increased **chromosome breakage** [1]. - It is associated with **bone marrow failure** and development of various malignancies. *Bloom syndrome* - Bloom syndrome results from defects in the **BLM gene**, leading to **genomic instability** and an increased rate of chromosome breakage [1]. - This condition causes symptoms like **short stature**, **facial lesions**, and a predisposition to cancer. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 322-323.

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