Molecular Pathology — MCQs

Molecular Pathology Indian Medical PG Practice Questions and MCQs

Question 201: Which of the following is true? 1. BRCA1 is an oncogene 2. HER2neu is amplified only in a fraction of breast cancer 3. EGFR (+) is seen in non-small cell lung cancer 4. N-MYC is a tumor suppressor gene

A. 1,3
B. 1,2
C. 2,3 (Correct Answer)
D. All of the options

Explanation: ***Correct Option: 2,3*** - **Statement 2 is TRUE**: HER2neu amplification occurs in only a fraction (~15-20%) of breast cancers, making it a specific subset requiring targeted therapy with trastuzumab (Herceptin) [1]. - **Statement 3 is TRUE**: EGFR (epidermal growth factor receptor) mutations or overexpression are commonly seen in non-small cell lung cancer (NSCLC) and serve as important therapeutic targets for tyrosine kinase inhibitors. *Incorrect Option: 1,3* - Statement 1 is **FALSE**: BRCA1 is a **tumor suppressor gene**, not an oncogene. It functions in DNA double-strand break repair, and loss-of-function mutations increase the risk of breast and ovarian cancers. - Statement 3 is TRUE, but the inclusion of the false statement about BRCA1 makes this option incorrect. *Incorrect Option: 1,2* - Statement 1 is **FALSE**: BRCA1 is a **tumor suppressor gene**, not an oncogene. - Statement 2 is TRUE [1], but the false classification of BRCA1 invalidates this option. *Incorrect Option: All of the options* - Statement 1 is **FALSE**: BRCA1 is a tumor suppressor gene, not an oncogene. - Statement 4 is **FALSE**: N-MYC is an **oncogene** that is amplified in neuroblastoma and other cancers, not a tumor suppressor gene. - Since two of the four statements are incorrect, "All of the options" cannot be true. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, pp. 1059-1060.

Question 202: Barr body is NOT seen in:

A. Marfan's syndrome
B. Turner syndrome (Correct Answer)
C. Down's syndrome
D. Klinefelter syndrome

Explanation: ***Turner syndrome*** - Females with **Turner syndrome** have a **45, X0 karyotype**, meaning they only have one X chromosome [1]. - The **Barr body** is formed by the inactivation of one of the two X chromosomes in females, so its absence indicates only one X chromosome [1]. *Marfan's syndrome* - **Marfan's syndrome** is an autosomal dominant disorder affecting connective tissue, caused by a mutation in the **FBN1 gene** on chromosome 15. - The presence or absence of a Barr body is not directly related to Marfan's syndrome as it affects both males and females, and females would still have a Barr body. *Down's syndrome* - **Down's syndrome** is caused by **trisomy 21**, an extra copy of chromosome 21. - The presence or absence of a Barr body is determined by the number of X chromosomes, and individuals with Down's syndrome, if female, would still have a Barr body. *Klinefelter syndrome* - Individuals with **Klinefelter syndrome** have a **47, XXY karyotype**, possessing at least two X chromosomes and one Y chromosome. - This condition is characterized by the presence of a **Barr body** due to the inactivation of one of the multiple X chromosomes. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 175-177.

Question 203: Which of the following childhood tumor uses N-myc gene amplification for its prognosis?

A. Neuroblastoma (Correct Answer)
B. Nephroblastoma
C. Retinoblastoma
D. Rhabdomyosarcoma

Explanation: ***Neuroblastoma*** - **N-myc gene amplification** is a crucial **prognostic indicator** in neuroblastoma, correlating with aggressive disease and poor outcomes [1]. - Neuroblastoma is a **childhood cancer of neural crest origin**, often presenting as an adrenal mass or in sympathetic ganglia. *Nephroblastoma* - Also known as **Wilms tumor**, it is a childhood kidney cancer. - Its prognosis is more strongly associated with histology (e.g., **anaplasia**) and specific gene mutations like **WT1**, not N-myc amplification. *Retinoblastoma* - This is a **childhood eye cancer**. - Its prognosis is primarily linked to the presence of **RB1 gene mutations** and the extent of retinoblastoma gene protein (pRB) expression, not N-myc. *Rhabdomyosarcoma* - An aggressive **childhood soft tissue sarcoma** with skeletal muscle differentiation. - Prognostic factors often include clinical staging, histology (e.g., **alveolar vs. embryonal**), and specific genetic translocations like **PAX-FOXO1**, rather than N-myc amplification. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of Infancy and Childhood, pp. 486-487.

Question 204: The component of cell most affected by radiation?

A. Cell wall
B. Cell membrane
C. DNA (Correct Answer)
D. Cytoplasm

Explanation: ***DNA*** - **DNA** is the primary target for radiation-induced damage due to its critical role in cellular function and its complex structure, making it susceptible to breaks and mutations [1], [2]. - Damage to **DNA** can lead to **cell cycle arrest**, **apoptosis**, or **uncontrolled cell proliferation** (carcinogenesis) if not properly repaired [1], [2]. *Cell wall* - The **cell wall** is a rigid outer layer found in plants, fungi, and bacteria, not typically in human cells, and its primary role is structural support and protection, not a common target for direct radiation effects. - Animal cells, which are primarily affected by human-relevant radiation doses, lack a **cell wall**. *Cell membrane* - While the **cell membrane** can be affected by radiation, leading to changes in permeability and ion transport, these effects are generally secondary to **DNA damage** in terms of severe cellular consequences [2]. - The cell membrane primarily functions in **cell signaling** and **transport**, and direct damage often requires higher radiation doses to cause significant cellular death compared to DNA. *Cytoplasm* - The **cytoplasm** contains various organelles and cytosol, and while radiation can cause **oxidative stress** and damage to cytoplasmic components, the most critical and irreparable damage is typically to the **DNA** within the nucleus [2]. - Damage to cytoplasmic components often has less severe and more readily repairable consequences for cell survival compared to direct nuclear DNA damage. **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. 101-102. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Central Nervous System Synapse, pp. 436-439.

Question 205: Number of chromosomes in Klinefelter syndrome:

A. 44
B. 46
C. 47 (Correct Answer)
D. 45

Explanation: ***47*** - **Klinefelter syndrome** is a genetic condition in males characterized by the presence of an extra X chromosome, resulting in a **47, XXY karyotype** [1]. - This additional chromosome increases the total count from the typical 46 to **47** [1]. *44* - A count of 44 chromosomes would indicate either a severe **aneuploidy** or a **haploid** state, which is not compatible with human life in a full somatic cell. - Normal human somatic cells contain 46 chromosomes (2n). *46* - A count of 46 chromosomes represents the **normal diploid number** for human somatic cells (46, XX for females and 46, XY for males). - This count would signify a genetically typical individual, not someone with Klinefelter syndrome. *45* - A count of 45 chromosomes typically indicates a **monosomy**, such as **Turner syndrome** (45, X) in females, where one sex chromosome is missing. - This is a different chromosomal abnormality from Klinefelter syndrome, which involves an extra chromosome. **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. 92-93.

Question 206: Which of the following is not the karyotype of Turner syndrome?

A. 45 XO
B. 46,X,r(X)
C. 46,X,i(Xp) (Correct Answer)
D. 46,X, i(X) (q10)

Explanation: ***46,X,i(Xp)*** - This karyotype indicates an **isochromosome of the short arm of the X chromosome**, with two copies of Xp and complete loss of Xq. - This results in **duplication of Xp material** (including the critical SHOX gene region), which **prevents the characteristic short stature** of Turner syndrome [1]. - While Xq material is lost, the **presence of two Xp arms protects against the Turner phenotype**, making this karyotype **NOT typically associated with Turner syndrome**. Just as the loss of SHOX is associated with short stature, excess copies are associated with tall stature [1]. - This is an extremely rare karyotype that does not produce the classic Turner syndrome features. *45,XO* - This is the **classic and most common karyotype for Turner syndrome** (about 50-60% of cases), characterized by complete absence of one X chromosome. - Results in characteristic features: **short stature, gonadal dysgenesis, webbed neck, cardiac anomalies**, and lymphedema. *46,X,r(X)* - This karyotype has a **ring X chromosome**, where both ends of the X chromosome have fused together, typically with loss of genetic material from both arms. - The loss of critical genes leads to **Turner syndrome phenotype** due to haploinsufficiency. - Ring X chromosomes account for approximately 5% of Turner syndrome cases. *46,X,i(X)(q10)* - This is an **isochromosome of the long arm of the X chromosome** (i(Xq)), with two copies of Xq and complete loss of Xp [1]. - The **loss of Xp material (including SHOX gene)** causes the characteristic **short stature and skeletal abnormalities** of Turner syndrome [1]. - This is the **second most common structural abnormality** causing Turner syndrome (15-20% of cases). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 169-177.

Question 207: Subtelomeric rearrangement of genes is frequently associated with intellectual disability. All of the following techniques can be used to diagnose them except:

A. MALDI (Correct Answer)
B. FISH
C. MAPH
D. cGH array

Explanation: ***MALDI*** - **Matrix-assisted laser desorption/ionization (MALDI)** is a soft ionization technique used in mass spectrometry for analyzing biomolecules like proteins and peptides. - It is not suitable for detecting large-scale chromosomal rearrangements such as **subtelomeric deletions or duplications**. *FISH* - **Fluorescence in situ hybridization (FISH)** uses fluorescent DNA probes that bind to specific target regions on chromosomes, allowing for the detection of deletions or duplications [1]. - **Subtelomeric FISH** specifically targets the ends of chromosomes and is a common method for identifying subtelomeric rearrangements [1]. *MAPH* - **Multiplex amplifiable probe hybridization (MAPH)** is a technique used for detecting copy number variations (CNVs), including deletions and duplications, in specific genomic regions. - It can be applied to **subtelomeric regions** by designing probes specific to those areas, making it useful for diagnosing subtelomeric rearrangements. *CGH array* - **Comparative genomic hybridization array (CGH array)** is a high-resolution method that compares the patient's DNA to a control DNA to detect unbalanced chromosomal abnormalities across the entire genome [1]. - It is highly effective in identifying **copy number changes**, including subtelomeric deletions and duplications, associated with intellectual disability [1], [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 186-187. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 187.

Question 208: Molecular genetic testing is used to detect all of the following except?

A. Deletion
B. Translocation (Correct Answer)
C. Amplification
D. Point mutation

Explanation: ***Translocation*** - **Translocations** are chromosomal rearrangements that were historically detected primarily by **cytogenetic methods** (karyotyping, conventional FISH), rather than by traditional molecular genetic testing methods focused on DNA sequencing [3]. - While modern molecular techniques like **RT-PCR for fusion transcripts** (e.g., BCR-ABL), **NGS-based fusion detection**, and **targeted breakpoint sequencing** can now detect translocations, the classic distinction is that translocations involve large-scale structural chromosomal changes better visualized by cytogenetics [2], [3]. - In the traditional classification, molecular genetic testing referred primarily to **sequence-based methods** (PCR, Sanger sequencing) that detect smaller-scale DNA changes rather than gross chromosomal rearrangements. *Deletion* - **Deletions** are readily detected by molecular genetic testing using PCR, Sanger sequencing, MLPA (Multiplex Ligation-dependent Probe Amplification), and NGS [5]. - These techniques identify missing DNA sequences by analyzing changes in fragment size, read depth, or absence of expected amplification products [2], [5]. *Amplification* - **Amplification** (increased gene copy number) is detected by molecular methods including **quantitative PCR (qPCR)**, **digital PCR**, and **NGS-based copy number analysis** [4]. - These techniques quantify gene copy numbers to identify amplifications like HER2 amplification in breast cancer. *Point mutation* - **Point mutations** are the primary target of classic molecular genetic testing [1]. - Detected by **Sanger sequencing**, **allele-specific PCR**, **NGS panels**, and other sequence-based methods that identify single nucleotide changes in DNA [1], [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 185. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 185-186. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 342-343. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 344. [5] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 183-184.

Question 209: What is the most common genetic abnormality in cystic fibrosis?

A. ΔF508 (Correct Answer)
B. R117H
C. G551D
D. G542X

Explanation: ***ΔF508*** - This mutation accounts for approximately **70% of all cystic fibrosis (CF) cases** worldwide, making it the most common genetic abnormality [1]. - It results in the deletion of a **phenylalanine residue** at position 508 in the **CFTR protein**, leading to misfolding and degradation [1]. *R117H mutation* - This is a rare **splice-site mutation** that can cause a milder form of CF or CFTR-related disorders. - It results in reduced CFTR protein function but is not the most common mutation. *G551D mutation* - This mutation is a **class III gating mutation**, meaning it impairs the opening of the **chloride channel** rather than its synthesis or trafficking. - It is relatively rare and is specifically targeted by CFTR modulator therapies like ivacaftor. *G542X mutation* - This is a **class I nonsense mutation** that introduces a premature stop codon, leading to a truncated and non-functional CFTR protein [1]. - While it causes severe CF, it is less common than the ΔF508 mutation. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of Infancy and Childhood, p. 476.

Question 210: FISH can detect all except:

A. Point mutation (Correct Answer)
B. Deletion
C. Amplification
D. Translocation

Explanation: ***Point mutation*** - **FISH (Fluorescence In Situ Hybridization)** is a cytogenetic technique used to detect **chromosomal abnormalities** by visualizing specific DNA sequences [3]. A point mutation involves a single nucleotide change, which is too small to be detected by FISH [1]. - Techniques like **DNA sequencing** or **PCR-based methods** are required to identify point mutations. *Deletion* - FISH can effectively detect **deletions** of significant size (typically several kilobases or larger) in a chromosome by noting the absence of a fluorescent signal from a probe designed to bind to the deleted region [1]. - This is commonly used in congenital disorders or cancer to identify regions of **genomic loss**. *Amplification* - **Gene amplification** involves an increased number of copies of a specific gene or chromosomal region. FISH can detect this by showing multiple, clustered fluorescent signals when using a probe specific to the amplified region [2]. - A classic example is **HER2 gene amplification** in breast cancer, which guides treatment decisions [2]. *Translocation* - **Chromosomal translocations**, where a segment of one chromosome breaks off and attaches to another chromosome, can be readily identified by FISH [3]. This is done using specific probes that generate distinct fusion signals or abnormal signal patterns. - **BCR-ABL fusion** in chronic myeloid leukemia (CML) is a well-known example detected by FISH [3]. **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. 58-59. [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. 256-257. [3] 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. 225-226.

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Principles of Molecular Pathology

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DNA and RNA Analysis Techniques

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Next-Generation Sequencing

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Molecular Diagnosis of Infectious Diseases

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Molecular Oncology

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Pharmacogenomics

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Genetic Counseling and Risk Assessment

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Molecular Diagnostics Quality Control

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