Molecular Pathology Practice Questions

Q: Which one of the following is an autosomal recessive disorder?

Albinism. ***Albinism*** - **Albinism** is an **autosomal recessive disorder** characterized by a partial or complete lack of melanin pigment in the skin, hair, and eyes [1], [2]. - This condition is inherited when an individual receives **two copies of the defective gene**, one from each parent [1]. *Huntington's disease* - **Huntington's disease** is an **autosomal dominant disorder**, meaning only one copy of the mutated gene is sufficient to cause the disease. - It is characterized by progressive neurodegeneration, leading to uncontrolled movements, cognitive decline, and psychiatric problems. *Marfan's syndrome* - **Marfan's syndrome** is an **autosomal dominant disorder** affecting connective tissue, primarily impacting the skeletal, ocular, and cardiovascular systems. - It results from a mutation in the **FBN1 gene** which encodes for fibrillin-1, a component of elastic fibers. *Neurofibromatosis-1* - **Neurofibromatosis type 1 (NF1)** is an **autosomal dominant disorder** caused by a mutation in the NF1 gene, leading to the growth of tumors along nerves. - Clinical features include **café-au-lait spots**, neurofibromas, and Lisch nodules. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 150-151. [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. 119-120.

Q: Which of the following is the most common mutation in Ewing's sarcoma?

Translocation 11; 22. **Translocation 11; 22** - The most common and characteristic genetic alteration in **Ewing's sarcoma** is a **balanced chromosomal translocation** between chromosomes 11 and 22, specifically **t(11;22)(q24;q12)**. - This translocation results in the fusion of the **EWS gene** (on chromosome 22) with the **FLI1 gene** (on chromosome 11), creating a novel **fusion oncogene (EWS-FLI1)** that drives tumor development. *Translocation X : 18* - This translocation, **t(X;18)(p11.2;q11.2)**, is characteristic of **synovial sarcoma**, a distinct soft tissue tumor, not Ewing's sarcoma. - It leads to the fusion of the **SS18 gene** with one of several **SSX genes** (SSX1, SSX2, or SSX4). *Activating mutation of cell surface protein* - While activating mutations in various genes can occur in cancers, a general statement about an "activating mutation of a cell surface protein" is not the specific, most common genetic hallmark for **Ewing's sarcoma**. - Ewing's sarcoma is defined by its characteristic **fusion oncogene**. *Missense mutation in EXTI* - A **missense mutation in EXTI** (exostosin glycosyltransferase 1) is associated with **hereditary multiple exostoses** (also known as multiple osteochondromas), a different genetic disorder. - This mutation is not a defining characteristic or common mutation found in **Ewing's sarcoma**.

Q: Li-Fraumeni syndrome occurs due to mutation in which gene?

TP53. ***Correct Answer: TP53*** - Li-Fraumeni syndrome is an autosomal dominant hereditary cancer syndrome linked to germline mutations in the **TP53 tumor suppressor gene**. - The TP53 gene encodes the **p53 protein**, a critical regulator of the cell cycle and apoptosis, often called the "guardian of the genome." *Incorrect: CDKN2A* - Mutations in the **CDKN2A gene** are primarily associated with familial melanoma and pancreatic cancer. - This gene encodes two tumor suppressor proteins, **p16INK4a** and **p14ARF**, which regulate the cell cycle. *Incorrect: PTEN* - The **PTEN gene** is associated with Cowden syndrome, which increases the risk of benign and malignant tumors in various tissues, including breast, thyroid, and endometrium. - PTEN is a tumor suppressor gene involved in cell growth, proliferation, and apoptosis. *Incorrect: MDM2* - The **MDM2 gene** is an oncogene that inactivates the p53 tumor suppressor protein. - While it interacts with p53, MDM2 mutations or overexpression are not the primary cause of Li-Fraumeni syndrome; rather, they contribute to cancer development by inhibiting p53 function.

Q: What is the chromosomal defect associated with Prader-Willi syndrome?

Chromosome 15. ***Chromosome 15*** - **Prader-Willi syndrome** is characterized by a deletion or other abnormality on the **paternal copy** of **chromosome 15q11-q13** [1]. - This specific region contains genes critical for normal development and function, whose altered expression due to the paternal origin causes the syndrome [1]. *Chromosome 5* - Abnormalities of chromosome 5 are associated with conditions like **Cri-du-chat syndrome**, which involves a deletion on the short arm (5p). - This is not linked to the characteristic symptoms of Prader-Willi syndrome. *Chromosome 10* - Defects on chromosome 10 are associated with various other genetic disorders, such as **multiple endocrine neoplasia type 2 (MEN 2)** or **Cowden syndrome**. - There is no established direct link between chromosome 10 abnormalities and Prader-Willi syndrome. *Chromosome 21* - **Trisomy 21** is the genetic defect responsible for **Down syndrome** (presence of an extra copy of chromosome 21) [2]. - While a common chromosomal abnormality, it presents with a distinct set of clinical features different from Prader-Willi syndrome [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 182-183. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 171-172.

Q: Which gene is primarily associated with Cowden syndrome?

PTEN. ***PTEN*** - Cowden syndrome is an **autosomal dominant** inherited disorder caused by germline mutations in the **PTEN (phosphatase and tensin homolog) tumor suppressor gene**. - The PTEN gene plays a crucial role in cell growth, proliferation, and apoptosis, and its dysfunction leads to uncontrolled cell growth and the development of multiple **hamartomas** and increased cancer risk. *TP53* - Mutations in the **TP53 gene** are primarily associated with Li-Fraumeni syndrome, a different inherited cancer predisposition syndrome characterized by a high risk of various cancers including sarcomas, breast cancer, and adrenocortical carcinoma. - While both inherited cancer syndromes involve tumor suppressor gene mutations, the specific gene affected and the clinical presentation differ significantly. *RB1* - The **RB1 gene** is a tumor suppressor gene primarily associated with **retinoblastoma**, a rare childhood eye cancer, and an increased risk of other cancers like osteosarcoma. - It plays a critical role in cell cycle regulation, and its mutation leads to uncontrolled cell division in the retina and other tissues. *KRAS* - The **KRAS gene** is an oncogene, not a tumor suppressor gene, and its mutations are frequently found in various sporadic cancers, particularly **colorectal cancer**, pancreatic cancer, and lung cancer. - KRAS mutations lead to constitutive activation of signaling pathways that promote cell growth and survival, but they are not the primary genetic cause of inherited Cowden syndrome.

Q: Which of the following genes primarily promotes apoptosis (programmed cell death)?

Bax. ***Bax*** - **Bax** is a **pro-apoptotic gene** that actively promotes programmed cell death by forming channels in the mitochondrial outer membrane, leading to cytochrome c release and activation of caspases [1]. - It is a key member of the Bcl-2 family and plays a critical role in the **intrinsic apoptotic pathway** [2]. - Unlike the other options, Bax **promotes** rather than inhibits apoptosis [1]. *Bclx* - **Bcl-xL** is an **anti-apoptotic** gene that **inhibits** cell death by preventing the activation of pro-apoptotic proteins like Bax [1]. - It maintains mitochondrial membrane integrity, thereby **blocking** apoptosis [1]. *Mcl* - **Mcl-1** (Myeloid cell leukemia sequence 1) is an **anti-apoptotic** gene belonging to the Bcl-2 family [1]. - Its primary role is to **inhibit** apoptosis and promote cell survival by sequestering pro-apoptotic proteins [1]. *Bcl2* - **Bcl-2** (B-cell lymphoma 2) is the prototype **anti-apoptotic** gene that **prevents** programmed cell death [3]. - It functions by binding to and inhibiting pro-apoptotic members of the Bcl-2 family, thus maintaining cell viability and **opposing** apoptosis [3]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 310. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death, pp. 64-67. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 310-311.

Question 1

In the context of molecular diagnostics, which method is the best for detecting chromosomal translocations?

Accepted Answer

FISH

Answer

Array CGH

Answer

Karyotyping

Answer

Sanger Sequencing

Question 2

What is the consequence of defects in DNA repair enzymes on genomic stability in cancer development?

Accepted Answer

Increased mutation rate due to genomic instability.

Answer

Enhanced DNA repair mechanisms.

Answer

Increased cell survival.

Answer

Increased cellular differentiation.

Question 3

Which one of the following is an autosomal recessive disorder?

Accepted Answer

Albinism

Answer

Marfan’s syndrome

Answer

Neurofibromatosis-1

Answer

Huntington's disease

Question 4

Which of the following is the most common mutation in Ewing's sarcoma?

Accepted Answer

Translocation 11; 22

Answer

Translocation X : 18

Answer

Missense mutation in EXT1

Answer

Activating mutation of cell surface protein

Question 5

Which of the following statements about FISH (Fluorescence In Situ Hybridization) is false?

Accepted Answer

Requires DNA polymerase

Answer

Used to detect copy number variations

Answer

Used to detect balanced translocations

Answer

Requires fluorescent probes

Question 6

Li-Fraumeni syndrome occurs due to mutation in which gene?

Accepted Answer

TP53

Answer

CDKN2A

Answer

PTEN

Answer

MDM2

Question 7

What is the chromosomal defect associated with Prader-Willi syndrome?

Accepted Answer

Chromosome 15

Answer

Chromosome 5

Answer

Chromosome 10

Answer

Chromosome 21

Question 8

Diagnose the disorder by looking at the karyotype.

Accepted Answer

Down syndrome.

Answer

Patau syndrome.

Answer

Turner syndrome.

Answer

Klinefelter syndrome.

Question 9

Which gene is primarily associated with Cowden syndrome?

Accepted Answer

PTEN

Answer

RB1

Answer

KRAS

Answer

TP53

Question 10

Which of the following genes primarily promotes apoptosis (programmed cell death)?

Accepted Answer

Bax

Answer

Bclx

Answer

Mcl

Answer

Bcl2

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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