Robbins Basic Pathology
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
1
Reference – Ch. 1 — The Genome
Question Stem: A newborn’s whole-genome sequencing shows
multiple variants in noncoding DNA regions near a gene
controlling cardiac development. Which cellular mechanism
best explains how these noncoding variants could alter gene
expression without changing protein sequence?
A. Frameshift mutations in exons causing premature stop
codons
,B. Altered chromatin modification and enhancer activity
changing transcriptional regulation
C. Increased mitochondrial DNA copy number altering energy
supply to cardiomyocytes
D. Proteasomal degradation of transcription factors leading to
loss of function
Correct Answer: B
Rationales:
• Correct (B): Noncoding DNA (including enhancers,
promoters, and regulatory elements) and chromatin
modifications modulate gene transcription; variants here
can change enhancer activity or histone marks and thus
gene expression without altering protein coding sequence.
• Incorrect (A): Frameshifts occur in coding exons and
change protein sequence — not applicable to noncoding
regulatory variants.
• Incorrect (C): Mitochondrial DNA copy number affects
cellular energetics but does not directly mediate cis-
regulatory effects in nuclear noncoding DNA.
• Incorrect (D): Proteasomal degradation affects protein
turnover but does not explain sequence variants in
noncoding DNA altering transcription.
Teaching Point: Noncoding DNA variants can alter gene
expression via chromatin and enhancer effects.
,Citation: Kumar et al. (2017). Robbins Basic Pathology (10th
Ed.). Ch. 1.
2
Reference – Ch. 1 — The Genome
Question Stem: A patient’s tumor shows hypomethylation
across repetitive DNA and focal hypermethylation at a tumor
suppressor gene promoter. Which genomic/epigenetic
consequence is most consistent with these findings?
A. Global transcriptional silencing and increased genomic
stability
B. Increased expression of oncogenes and silencing of tumor
suppressor genes
C. Direct alteration of amino acid sequence in tumor suppressor
proteins
D. Increased proteasomal degradation of methylated DNA-
binding proteins
Correct Answer: B
Rationales:
• Correct (B): Global hypomethylation can activate normally
silent sequences (e.g., oncogene expression, genomic
instability) while promoter hypermethylation can silence
tumor suppressor genes — a common cancer epigenetic
pattern.
, • Incorrect (A): Hypomethylation tends to increase
transcription and genomic instability rather than silencing.
• Incorrect (C): Methylation alters gene expression, not the
amino acid sequence of proteins.
• Incorrect (D): Proteasomal degradation is unrelated to
DNA methylation status per se.
Teaching Point: Cancer often shows global hypomethylation
plus promoter hypermethylation of tumor suppressors.
Citation: Kumar et al. (2017). Robbins Basic Pathology (10th
Ed.). Ch. 1.
3
Reference – Ch. 1 — The Genome
Question Stem: A clinician interprets a patient’s microRNA
(miRNA) profile showing elevated miRNAs that target an mRNA
encoding a pro-apoptotic protein. What is the expected effect
on the cell?
A. Enhanced translation of the pro-apoptotic protein and
increased apoptosis
B. Post-transcriptional repression of the pro-apoptotic protein
and reduced apoptosis
C. Increased genomic instability due to miRNA-mediated DNA
breaks
D. Activation of mitochondrial ATP synthesis
Correct Answer: B
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
1
Reference – Ch. 1 — The Genome
Question Stem: A newborn’s whole-genome sequencing shows
multiple variants in noncoding DNA regions near a gene
controlling cardiac development. Which cellular mechanism
best explains how these noncoding variants could alter gene
expression without changing protein sequence?
A. Frameshift mutations in exons causing premature stop
codons
,B. Altered chromatin modification and enhancer activity
changing transcriptional regulation
C. Increased mitochondrial DNA copy number altering energy
supply to cardiomyocytes
D. Proteasomal degradation of transcription factors leading to
loss of function
Correct Answer: B
Rationales:
• Correct (B): Noncoding DNA (including enhancers,
promoters, and regulatory elements) and chromatin
modifications modulate gene transcription; variants here
can change enhancer activity or histone marks and thus
gene expression without altering protein coding sequence.
• Incorrect (A): Frameshifts occur in coding exons and
change protein sequence — not applicable to noncoding
regulatory variants.
• Incorrect (C): Mitochondrial DNA copy number affects
cellular energetics but does not directly mediate cis-
regulatory effects in nuclear noncoding DNA.
• Incorrect (D): Proteasomal degradation affects protein
turnover but does not explain sequence variants in
noncoding DNA altering transcription.
Teaching Point: Noncoding DNA variants can alter gene
expression via chromatin and enhancer effects.
,Citation: Kumar et al. (2017). Robbins Basic Pathology (10th
Ed.). Ch. 1.
2
Reference – Ch. 1 — The Genome
Question Stem: A patient’s tumor shows hypomethylation
across repetitive DNA and focal hypermethylation at a tumor
suppressor gene promoter. Which genomic/epigenetic
consequence is most consistent with these findings?
A. Global transcriptional silencing and increased genomic
stability
B. Increased expression of oncogenes and silencing of tumor
suppressor genes
C. Direct alteration of amino acid sequence in tumor suppressor
proteins
D. Increased proteasomal degradation of methylated DNA-
binding proteins
Correct Answer: B
Rationales:
• Correct (B): Global hypomethylation can activate normally
silent sequences (e.g., oncogene expression, genomic
instability) while promoter hypermethylation can silence
tumor suppressor genes — a common cancer epigenetic
pattern.
, • Incorrect (A): Hypomethylation tends to increase
transcription and genomic instability rather than silencing.
• Incorrect (C): Methylation alters gene expression, not the
amino acid sequence of proteins.
• Incorrect (D): Proteasomal degradation is unrelated to
DNA methylation status per se.
Teaching Point: Cancer often shows global hypomethylation
plus promoter hypermethylation of tumor suppressors.
Citation: Kumar et al. (2017). Robbins Basic Pathology (10th
Ed.). Ch. 1.
3
Reference – Ch. 1 — The Genome
Question Stem: A clinician interprets a patient’s microRNA
(miRNA) profile showing elevated miRNAs that target an mRNA
encoding a pro-apoptotic protein. What is the expected effect
on the cell?
A. Enhanced translation of the pro-apoptotic protein and
increased apoptosis
B. Post-transcriptional repression of the pro-apoptotic protein
and reduced apoptosis
C. Increased genomic instability due to miRNA-mediated DNA
breaks
D. Activation of mitochondrial ATP synthesis
Correct Answer: B
