Molecular Pathology Practice Questions

Q: Li–Fraumeni syndrome is associated with mutations in which of the following genes?

Gene TP53. ***Gene TP53*** - Li-Fraumeni syndrome is a rare, inherited cancer susceptibility syndrome associated with germline mutations in the **TP53 tumor suppressor gene**. - The **TP53 gene** encodes the p53 protein, which plays a critical role in cell cycle arrest, DNA repair, and initiation of apoptosis in response to cellular stress, thus preventing tumor formation. *Gene P21* - The **p21 gene** (CDKN1A) is a cyclin-dependent kinase inhibitor that acts downstream of p53, mediating p53-induced cell cycle arrest. - While p21 is involved in the p53 pathway, mutations in p21 itself are not the primary cause of Li-Fraumeni syndrome. *Gene RB1* - The **RB1 gene** encodes the retinoblastoma protein, a tumor suppressor involved in cell cycle regulation, particularly in controlling passage from G1 to S phase. - Mutations in **RB1** are primarily associated with hereditary retinoblastoma and osteosarcoma, not Li-Fraumeni syndrome. *Gene BRCA1* - The **BRCA1 gene** is a tumor suppressor gene involved in DNA repair, especially homologous recombination. - Germline mutations in **BRCA1** are strongly associated with hereditary breast and ovarian cancer syndrome, not Li-Fraumeni syndrome.

Q: Sex chromosome pattern in Klinefelter's syndrome is:

XXY. ***XXY*** - Klinefelter's syndrome is a **chromosomal disorder** that affects males, resulting from the presence of an extra X chromosome [2]. - The typical sex chromosome pattern is **XXY**, leading to a total of 47 chromosomes (47, XXY) [2]. - Clinical features include **tall stature**, **gynecomastia**, **small firm testes**, **infertility**, and **decreased testosterone** levels [2]. *XO* - This chromosomal pattern (45, XO) is characteristic of **Turner syndrome**, which affects females [1]. - Individuals with Turner syndrome typically present with **short stature**, **ovarian dysgenesis**, and a **webbed neck** [1]. *XX* - This is the normal sex chromosome pattern for a **female** (46, XX). - Females with this pattern typically develop normal **secondary sexual characteristics** and reproductive functions. *XY* - This is the normal sex chromosome pattern for a **male** (46, XY). - Males with this pattern typically develop normal **secondary sexual characteristics** and reproductive functions. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 173-174. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 174-175.

Q: Which malformation is associated with mutations in the HOX gene?

Polysyndactyly. ***Polysyndactyly*** - The **HOX gene** plays a critical role in limb development and is associated with the malformation of **polysyndactyly**, which is characterized by extra fingers or toes [1]. - This condition is due to the disruption of the normal **patterning** during limb formation, directly involving the action of HOX genes [1]. *Gorlin syndrome* - Gorlin syndrome is primarily caused by mutations in the **PTCH1 gene**, linked to **basal cell carcinoma** and other abnormalities. - It does not involve HOX gene mutations, hence is **not** related to limb malformations. *Holoprosencephaly* - Holoprosencephaly is a developmental condition often linked to **chromosomal anomalies** and abnormal embryonic development, **not specifically** HOX gene mutations. - It refers to the incomplete separation of the forebrain, distinct from the **limb malformations** associated with HOX genes. *Mayer Rokitansky syndrome* - Mayer-Rokitansky syndrome involves **agenesis** or **hypoplasia** of the uterus and upper two-thirds of the vagina, which is due to other genetic factors. - This condition is not related to the functions of the **HOX genes** in limb or skeletal development. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, p. 1186.

Q: Which tumor is not associated with von Hippel-Lindau disease?

Cholangiocarcinoma. ***Cholangiocarcinoma*** - Cholangiocarcinoma is a **bile duct cancer** that is not typically associated with **von Hippel-Lindau (VHL) disease**. - While VHL disease affects various organs through abnormal blood vessel growth, the **bile ducts** are not common sites for VHL-related tumors. *Hemangioblastoma of Cerebellum* - **Hemangioblastomas**, particularly in the **cerebellum**, are characteristic benign tumors strongly associated with **VHL disease**. - These tumors are highly vascular and linked to mutations in the **VHL tumor suppressor gene** [2]. *Renal Cell Carcinoma* - **Clear cell renal cell carcinoma** is a major manifestation of VHL disease due to a mutated **VHL gene**, which affects oxygen sensing and leads to tumor formation [1]. - Patients with VHL disease have a significantly increased risk of developing **renal cysts** and these specific kidney cancers. *Pheochromocytoma* - **Pheochromocytomas**, which are neuroendocrine tumors of the **adrenal medulla**, are a well-documented feature of VHL disease. - They produce **catecholamines** and can lead to hypertension and other symptoms related to hormonal excess. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Kidney, pp. 958-959. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 306-307.

Q: Which of the following is a characteristic feature of Down syndrome?

Trisomy 21. ***Trisomy 21*** - **Down syndrome** is the most common autosomal chromosome abnormality and is characterized by the presence of an extra copy of chromosome 21 [1, 2]. - This extra genetic material leads to the characteristic physical features, intellectual disability, and medical conditions associated with the syndrome [1, 2]. *Trisomy 18* - **Trisomy 18**, also known as **Edwards syndrome**, is a serious chromosomal disorder distinct from Down syndrome [2]. - It is characterized by severe developmental problems, including **heart defects**, **kidney malformations**, and **severe intellectual disability**, with generally a much shorter life expectancy [2, 3]. *Robertsonian translocation involving chromosome 21* - A **Robertsonian translocation** involving chromosome 21 is a cause of Down syndrome, but it is not the characteristic feature itself; rather, it is a specific **chromosomal rearrangement** that can lead to an extra copy of chromosome 21 material [1, 2]. - This specific type of translocation accounts for only a small percentage (2-3%) of all Down syndrome cases, while **Trisomy 21** (nondisjunction) is the most common cause [1, 2]. *Trisomy 13* - **Trisomy 13**, also known as **Patau syndrome**, is a distinct chromosomal disorder characterized by the presence of an extra copy of chromosome 13 [2]. - It is associated with severe birth defects, including **cleft lip/palate**, **polydactyly**, and severe neurological problems, and is usually fatal within the first year of life [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 170-171. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 171-172. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 168-169.

Q: Which of the following cancers is least associated with BRCA2 mutations?

Vulval cancer. ***Vulval cancer*** - While there may be some rare, sporadic cases, **vulval cancer** is generally not considered a primary cancer with a strong, well-established association with **BRCA2 mutations**. - Its etiology is more commonly linked to **HPV infection** and other risk factors not directly related to hereditary breast and ovarian cancer syndromes. *Breast cancer* - **BRCA2 mutations** are strongly associated with an increased lifetime risk of developing **breast cancer**, particularly for **male breast cancer**. - These mutations impair DNA repair mechanisms, leading to genomic instability that can result in cancerous transformation of breast tissue. *Prostate cancer* - Men with **BRCA2 mutations** have a significantly elevated risk of developing **prostate cancer**, often at an earlier age and with a more aggressive phenotype. - This association is well-documented, making BRCA2 testing relevant in high-risk prostate cancer populations. *Ovarian cancer* - **BRCA2 mutations** are a significant risk factor for **ovarian cancer**, particularly **high-grade serous ovarian cancer**. - The risk is substantial, though generally lower than that conferred by BRCA1 mutations for ovarian cancer in particular.

Q: Barr body is absent in which individuals?

Turner. ***Turner*** - Individuals with **Turner syndrome (45,X)** have only one X chromosome and therefore no Barr bodies, as Barr bodies form from extra X chromosomes [1]. - This condition results in various clinical features including **short stature** and **gonadal dysgenesis** [1]. *Kleinfelter* - **Klinefelter syndrome (47, XXY)** typically presents with one or more Barr bodies due to the presence of an additional X chromosome [1]. - Affected individuals usually exhibit **hypogonadism** and **gynecomastia** [1]. *None of the above* - This option suggests that all listed conditions have Barr bodies, which is incorrect since Turner syndrome does not. - Hence, it fails to identify the true condition characterized by the **absence of Barr bodies**. *Super female* - Super female refers to individuals with **47, XXX** karyotype, who have one Barr body due to the two extra X chromosomes. - They often present with normal female characteristics, thus having Barr bodies. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 173-177.

Question 1

Li–Fraumeni syndrome is associated with mutations in which of the following genes?

Accepted Answer

Gene TP53

Answer

Gene RB1

Answer

Gene BRCA1

Answer

Gene P21

Question 2

Which syndrome is characterized by oro-cutaneous hamartomatous tumors, gastrointestinal polyps, and abnormalities of the breast, thyroid gland, and genitourinary system?

Accepted Answer

Cowden's syndrome - a genetic disorder involving multiple hamartomas and systemic abnormalities, including breast, thyroid, and genitourinary systems.

Answer

Juvenile polyposis - involves juvenile polyps in the gastrointestinal tract, without systemic hamartomas.

Answer

Peutz-Jeghers syndrome - features pigmented lesions and gastrointestinal hamartomas, without systemic involvement.

Answer

Familial adenomatous polyposis (FAP) - involves multiple adenomatous polyps and a high risk of colorectal cancer.

Question 3

Which investigation is the gold standard for diagnosing Edwards syndrome?

Accepted Answer

Karyotype

Answer

MLPA

Answer

Microarray

Answer

FISH

Question 4

Sex chromosome pattern in Klinefelter's syndrome is:

Accepted Answer

XXY

Answer

XO

Answer

XX

Answer

XY

Question 5

Which malformation is associated with mutations in the HOX gene?

Accepted Answer

Polysyndactyly

Answer

Holoprosencephaly

Answer

Mayer Rokitansky syndrome

Answer

Gorlin syndrome

Question 6

Which tumor is not associated with von Hippel-Lindau disease?

Accepted Answer

Cholangiocarcinoma

Answer

Renal Cell Carcinoma

Answer

Pheochromocytoma

Answer

Hemangioblastoma of Cerebellum

Question 7

Which of the following is a characteristic feature of Down syndrome?

Accepted Answer

Trisomy 21

Answer

Trisomy 18

Answer

Robertsonian translocation involving chromosome 21

Answer

Trisomy 13

Question 8

Which of the following cancers is least associated with BRCA2 mutations?

Accepted Answer

Vulval cancer

Answer

Breast cancer

Answer

Prostate cancer

Answer

Ovarian cancer

Question 9

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

Accepted Answer

Ataxia telangiectasia

Answer

Marfan's syndrome

Answer

Sickle cell disease

Answer

Klippel-Feil syndrome

Question 10

Barr body is absent in which individuals?

Accepted Answer

Turner

Answer

Super female

Answer

Klinefelter

Answer

None of the above

Molecular Pathology — MCQs

Molecular Pathology — MCQs

On this page

Practice by Chapter

Want unlimited practice?