Precancer Conditon Molecular Basis
Questions and Answers
- 1.
A 50-year-old nulliparous female presents with menorrhagia. An ultrasound examination reveals a polypoid mass in the fundus. The patient undergoes a hysterectomy, which reveals a poorly differentiated endometrial adenocarcinoma. The development of this neoplasm was preceded by which of the following changes in the glandular epithelium?
- A.
Atrophy
- B.
Hydropic swelling
- C.
Hyperplasia
- D.
Hypertrophy
- E.
Metaplasia
Correct Answer
C. HyperplasiaExplanation
C. Correct. Endometrial hyperplasia refers to a spectrum that ranges from simple glandular crowding to conspicuous proliferation of atypical glands. The risk of developing endometrial cancer increases with higher degrees of endometrial hyperplasia.Rate this question:
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- 2.
A 62-year-old man with a urinalysis revealing hematuria has cystoscopy performed, and an irregular erythematous area in the right dome is biopsied. Atypical transitional epithelial cells extend half the thickness of the epithelium, but not extending beneath the basement membrane:
- A.
Hyperplasia
- B.
Metaplasia
- C.
Dysplasia
- D.
Carcinoma in situ
- E.
Carcinoma
Correct Answer
C. DysplasiaExplanation
dysplasia - involves a part of the epithelium
carcinoma in situ
Dysplasia limited to epithelium
not yet invaded through basement membraneRate this question:
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- 3.
An 8-yr-old girl presents with multiple skin nodules on her face. A skin biopsy from one of the nodules shows a squamous cell carcinoma. Molecular biology reveals germline mutation in the gene encoding a nucleotide excision repair (NER) enzyme. Which of the following is the most likely diagnosis?
- A.
Ataxia telengiectasia
- B.
Li-Fraumeni syndrome
- C.
Xeroderma pigmentosum
- D.
Neurofibromatosis, type I
- E.
Fanconi anemia
Correct Answer
C. Xeroderma pigmentosumExplanation
C. Correct. Xeroderma pigmentosum is an autosomal recessive disease with an increased sensitivity to sunlight and a high incidence of skin cancers – squamous cell carcinoma, basal cell carcinoma and melanoma. The gene is involved in nucleotide excision repair (NER).Rate this question:
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- 4.
A 33-year-old female presents with a breast lump. Her sister and mother both had breast cancer. A mammogram shows an ill-defined density in the outer quadrant of left breast. Genetic screening identifies a mutation in the BRCA1. in addition to cell cycle control, BRCA1 protein promotes which of the following cellular functions?
- A.
Apoptosis
- B.
Cell adhesion
- C.
DNA repair
- D.
Gene transcription
Correct Answer
C. DNA repairExplanation
C. Correct. Breast cancer (BR) susceptibility genes (BRCA1 and BRCA2) encode tumor suppressor proteins involved in checkpoint functions related to progression of cell cycle into S phase. BRCA1 and BRCA2 proteins also promote DNA repair by binding to RAD51, a molecule that mediates DNA double-strand repair breaks.Rate this question:
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- 5.
A change in bowel habits prompts a 53-year-old woman to see her physician, who finds that the patient's stool is positive for occult blood. A colonoscopy is performed and reveals a 6 cm friable mass located in the cecum. A biopsy of this mass demonstrates a moderately differentiated adenocarcinoma. Which of the following findings is most likely to be present in this patient?
- A.
K-RAS mutation in neoplastic cells
- B.
Immuno-histochemical stain positive for vimentin in the neoplastic cells
- C.
Translocation between chromosomes 9 and 22
- D.
Translocation between chromosomes 8 and 14
Correct Answer
A. K-RAS mutation in neoplastic cellsExplanation
K-ras mutation is commonly seen in colon and pancreatic cancers.Rate this question:
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- 6.
A 67-year-old man presents with jaundice and weight loss. An abdominal CT scan shows a mass in the head of the pancreas. A biopsy is performed. The neoplastic cells analyzed from the tumor show continued activation of cytoplasmic kinases. Which of the following oncogenes is most likely to be involved?
- A.
MYC
- B.
APC
- C.
RAS
- D.
ERBB2
- E.
Sis
Correct Answer
C. RASExplanation
C. Correct. Mutations of RAS oncogene reduce GTPase activity, and RAS is bound in an activated GTP-bound state. RAS the signals through cytoplasmic kinases.
A. Incorrect. The MYC oncogene is a transcriptional activator that is overexpressed in tumors like neuroblastoma.
B. Incorrect. The APC gene can cause activation of the WNT signaling pathway.
D. Incorrect. The ERBB2 oncogene encoded growth factor receptors that are amplified in certain tumors like breast cancers.
E. Incorrect. The sis oncogene encodes PDGF-beta, which is overexpressed in some astrocytomas.Rate this question:
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- 7.
Which of the following mechanisms is most likely to be involved in the pathogenesis of this patient’s condition?
- A.
Point mutation
- B.
Chromosomal translocation
- C.
Gene amplification
- D.
Deletion
- E.
Epigenetic modification
Correct Answer
C. Gene amplificationExplanation
C. Correct. Mutations of RAS oncogene reduce GTPase activity, and RAS is bound in an activated GTP-bound state. RAS the signals through cytoplasmic kinasesRate this question:
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- 8.
Cytogenetic studies in malignant cells from a patient with AML-M3 demonstrate a chromosomal abnormality. Which of the following genes is most likely found at the translocation site?
- A.
ABL
- B.
BCL-1
- C.
BCL-2
- D.
MYC
- E.
Retinoic acid receptor (RAR)
Correct Answer
E. Retinoic acid receptor (RAR)Explanation
The correct answer is Retinoic acid receptor (RAR). AML-M3, also known as acute promyelocytic leukemia, is characterized by a specific chromosomal abnormality called the t(15;17) translocation. This translocation leads to the fusion of the PML gene on chromosome 15 and the RAR gene on chromosome 17. The fusion protein formed from this translocation, PML-RARα, plays a crucial role in the pathogenesis of AML-M3. Therefore, the most likely gene found at the translocation site in this case would be the Retinoic acid receptor (RAR) gene.Rate this question:
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- 9.
A 4-year-old African boy presents with a rapidly enlarging mass that involves the right side of his face. Based on the biopsy findings, a diagnosis of Burkitt lymphoma is made. Mutational activation of which of the following nuclear oncogenes is most likely to be present in this tumor?
- A.
ERBB2
- B.
P53
- C.
RAS
- D.
MYC
- E.
APC
Correct Answer
D. MYCExplanation
D. Correct. The MYC oncogene is commonly activated in Burkitt lymphoma because of a t(8;14) translocation. The MYC gene binds DNA to cause transcriptional activation of growth related genes, resulting in activation of cell cycle.
A. Incorrect. ERBB2 (or HER2) encodes growth factor receptor located on the cell surface.
B. Incorrect. P53 is a tumor suppressor gene that is inactivated in many cancers, including colon cancer (APC).
C. Incorrect. RAS oncogene encodes a GTP-binding protein that is located under the cell membrane.
E. Incorrect. APC is a tumor suppressor gene that is inactivated in many cancers, including colon cancer.Rate this question:
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- 10.
A 45-year-old man presents with fatigue and weight loss. Physical examination reveals a generalized non-tender lymphadenopathy and hepatosplenomegaly. A biopsy from the LN shows a malignant tumor of lymphoid cells. Immuno-histochemical staining of tumor cells with antibody to BCL2 is positive in the lymphocyte cell nuclei. Which of the following mechanisms has most likely produced the lymphoma?
- A.
Increased tyrosine kinase activity
- B.
Lack of apoptosis
- C.
Gene amplification
- D.
Reduced DNA repair
- E.
Loss of cell cycle inhibition
Correct Answer
B. Lack of apoptosisExplanation
B. Correct. Over-expression of BCL-2 gene prevents apoptosis, allowing accumulation of cells in lymphoid tissues.Rate this question:
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- 11.
The mother of a 5-year-old boy notices an enlarged abdomen. Physical examination reveals an ill-defined abdominal mass. A CT scan shows a 9-cm mass in the region of the adrenal gland. Surgical resection of the mass shows a neuroblastoma. Cytogenetic analysis shows many double minutes and homogenously staining region?
- A.
BCL1 (cyclin gene)
- B.
BCL2 (anti-apoptosis gene)
- C.
K-RAS (GTP-binding protein gene)
- D.
N-MYC (transcription factor gene)
- E.
P53 ( DNA damage response gene)
Correct Answer
D. N-MYC (transcription factor gene)Explanation
D. Correct. Double minutes and homogenously staining regions are seen on a karyotype represent gene amplifications. Amplification of N-MYC gene occurs in 30% to 40% of neuroblastomas and this change is associated with a poor prognosis.
A, Incorrect. BCL1 gene in mutated in mantle cell lymphoma (a non-Hodgkin lymphoma).
IB. ncorrect. BCL1 gene in mutated in follicular lymphoma (a non-Hodgkin lymphoma).
C. Incorrect. K-RAS mutation is present in many cancers, but not typically childhood cancers.
E. Incorrect. p53 mutation is present in many cancers, but not typically childhood cancers.Rate this question:
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- 12.
A 6-month-old girl is brought to the physician as the mother notices a mass on the left side of the child’s abdomen. Urinalysis shows high levels of vanillylmandelic acid (VMA). A CT scan shows an abdominal tumor with bony metastasis. Histological examination of the resected mass shows a neuroblastoma. Evaluation of the N-myc proto-oncogene in this child’s tumor will most likely demonstrate which of the following genetic changes
- A.
Chromosomal translocation
- B.
Exon deletion
- C.
Frame-shift mutation
- D.
Gene amplification
- E.
Expansion of a tri-nucleotide repeat
Correct Answer
D. Gene amplificationExplanation
D. Correct. The presence of N-myc HSRs is associated with up to 700-fold amplification of this gene and is a marker of advanced disease with a poor prognosis.Rate this question:
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- 13.
A 35-year-old man with a history of colon carcinoma undergoes a surveillance colonoscopy. It reveals hundreds of polyps in the colon and two focal 0.5 cm ulcerated areas. A biopsy from the ulcerated area reveals irregular glands penetrating the muscular layer. Which of the following molecular events is believed to occur very early in the evolution of his colonic disease process?
- A.
Mutation in mismatch repair genes
- B.
Inability to hydrolyze GTP-bound RAS
- C.
Activation of WNT signaling pathway
- D.
Loss of heterozygosity affecting p53 gene
- E.
Translocation of BCL2 from mitochondria to cytoplasm
Correct Answer
C. Activation of WNT signaling pathwayExplanation
C. Correct. This patient has a classical history of FAP with numerous polyps and a malignant transformation. The earliest event is loss of APC gene function. This prevents the destruction of beta-catenin in the cytoplasm, which translocates to the nucleus and co-activates the transcription of several genes. The APC ---- beta-catenin are components of the WNT signaling pathway.
A, Incorrect. This pathway is involved in HNPCC.
B. Incorrect. RAS activation occurs after the sequence is initiated by the APC gene.
D. Incorrect. Loss of cell cycle G1 arrest occurs with p53 late in the sequence.
E. Incorrect. BCL2 is not involved in the transition from adenoma to carcinoma.
f N-myc HSRs is associated with up to 700-fold amplification of this gene and is a marker of advanced disease with a poor prognosis.Rate this question:
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- 14.
A 76-year-old man presents with abdominal pain. An abdominal CT scan shows a 10-cm mass in the head of the pancreas. A biopsy shows an adenocarcinoma. Mutational analysis of the carcinoma cells show inactivation ofSMAD4 so that transcriptional activation of cyclin-dependent kinases with growth-suppressing effects is diminished. Which of the following regulatory pathways is most likely to be affected?
- A.
BCL2
- B.
Beta-catenin
- C.
MYC
- D.
P53
- E.
TGF-beta
Correct Answer
E. TGF-betaExplanation
E. Correct. TGF-beta inhibits cell proliferation by activation of growth-inhibiting genes, such as CDKIs. All pancreatic cancers and 83% of colon cancers have at least one mutational event in a TGF-beta pathway.Rate this question:
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- 15.
A 2-year-old boy is found to have bilateral retinal tumors. Molecular studies demonstrate a germline mutation in one allele of the Rb gene. Which of the following genetic events best explains the mechanism of carcinogenesis in this patient?
- A.
Balanced translocation
- B.
Expansion of tri-nucleotide repeat
- C.
Gene amplification
- D.
Loss of heterozygosity
- E.
Maternal non-disjunction
Correct Answer
D. Loss of heterozygosityExplanation
D. Correct. In hereditary retinoblastoma, an affected child inherits one defective Rb allele together with one normal gene. 50% of the normal gene product is sufficient to prevent the development of retinoblastoma. So, no observable changes are noted in the retina in this heterozygous state. However, if the remaining normal Rb allele is inactivated by deletion or mutation, the loss of its suppressor function leads to the appearance of a neoplasm. This genetic process is known as loss of heterozygosity.Rate this question:
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- 16.
A 55-year-old female presents with post-menopausal bleeding. The excised uterus on surgery shows a polypoid mass in the uterine fundus. Histology reveals a moderately differentiated adenocarcinoma. Neoplastic cells obtained from this patient would most likely show loss of function of which of the following cell cycle proteins?
- A.
P53
- B.
PTEN
- C.
Rb
- D.
RET
- E.
WT-1
Correct Answer
B. PTENExplanation
B. Correct. Loss of PTEN occurs in 2/3rds of endometrial carcinomas.Rate this question:
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- 17.
A 50-year-old female, who has a positive history of breast cancer presents with abdominal discomfort. Physical examination reveals a palpable adnexal mass and ascites. Further investigations reveal a papillary cystadenocarcinoma of the ovary. A mutation in which of the following structures is most likely associated with this patient’s malignant process?
- A.
BRCA1
- B.
P53
- C.
Rb
- D.
VHL
- E.
WT-1
Correct Answer
A. BRCA1Explanation
A. Correct. BRCA1 is implicated in hereditary breast cancers as well as familial papillary cystadenocarcinoma of ovary. Women who bear BRCA1 mutations tend to develop ovarian cancer earlier than women who have sporadic ovarian cancer, but their progress is considerably better.Rate this question:
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- 18.
Which of the following molecular alterations allows neoplastic cells with limitless replicative ability in vivo and vitro?
- A.
Activation of telomerase
- B.
Activation of BCL2 gene
- C.
Activation of VEGF
- D.
Inability to repair errors in DNA replication
- E.
Activation of cyclin gene
Correct Answer
A. Activation of telomeraseExplanation
A. Correct. Chromosomal telomere shortening in normal human cells limits their replicative potential and gives rise to replicative senescence. This occurs because most somatic cells lack the enzyme telomerase. 90% or more human tumor cells shows activation of telomerase. This explains the continuous growth of tumor in the body and immortalized cell lines.Rate this question:
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- 19.
Compared to normal cells, neoplastic cells would most likely show high levels of expression of which of the following proteins?
- A.
Desmin
- B.
Telomerase
- C.
P selectin
- D.
E cadherin
Correct Answer
B. TelomeraseExplanation
Neoplastic cells are characterized by uncontrolled growth and division, which is a hallmark of cancer. Telomerase is an enzyme that helps to maintain the length of telomeres, which are protective caps at the ends of chromosomes. Normal cells typically have low levels of telomerase expression, while neoplastic cells often have high levels. This increased expression allows neoplastic cells to continue dividing and avoid the natural process of cell death, contributing to their uncontrolled growth. Therefore, compared to normal cells, neoplastic cells are most likely to show high levels of telomerase expression.Rate this question:
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Current Version
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Mar 21, 2023Quiz Edited by
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Jun 18, 2012Quiz Created by
Chachelly
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