Molecular Genetic Pathology Flashcards

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

Answer: DNA mismatch repair deficiency

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

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

Answer: Testing matched normal tissue such as blood

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

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

Answer: Quantitative real-time RT-PCR

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

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

Answer: A heterozygous single-nucleotide variant

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

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

Answer: EGFR exon 19 deletion

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

In a Fragile X (FMR1) analysis, which molecular feature defines a full mutation?

Answer: More than 200 CGG repeats with hypermethylation

A full mutation is >200 CGG repeats, typically accompanied by promoter hypermethylation and gene silencing.

Digital droplet PCR offers an advantage over qPCR primarily because it provides:

Answer: Absolute quantification without a standard curve

By partitioning the sample into thousands of droplets, ddPCR counts target molecules absolutely without needing a standard curve.