ABPath Molecular Genetic Pathology 2

Question 1

A patient's tumor shows microsatellite instability (MSI-high). Which pathway defect is most directly responsible?

Accepted Answer

DNA mismatch repair deficiency

Answer

MSI results from loss of DNA mismatch repair function, commonly involving MLH1, MSH2, MSH6, or PMS2.

Question 2

Which method distinguishes germline BRCA1 mutations from somatic mutations in a tumor sample?

Accepted Answer

Testing matched normal tissue such as blood

Answer

A germline mutation is present in normal (blood) tissue, whereas a somatic mutation is confined to the tumor.

Question 3

The BCR-ABL1 fusion in chronic myeloid leukemia is best monitored for minimal residual disease using which assay?

Accepted Answer

Quantitative real-time RT-PCR

Answer

Quantitative RT-PCR on the fusion transcript provides sensitive quantification of BCR-ABL1 for MRD monitoring.

Question 4

A Sanger sequencing electropherogram shows a double peak at a single position in a heterozygous sample. This most likely represents:

Accepted Answer

A heterozygous single-nucleotide variant

Answer

Two overlapping peaks at one position reflect two alleles with different bases, i.e., a heterozygous SNV.

Question 5

Which alteration is the primary target of EGFR tyrosine kinase inhibitor therapy in non-small cell lung cancer?

Accepted Answer

EGFR exon 19 deletion

Answer

Exon 19 deletions and the L858R mutation are the classic activating EGFR alterations predicting TKI response.

American Board of Pathology (ABPath) Practice Test