Molecular Genetic Pathology Flashcards

The Philadelphia chromosome results from which translocation?

Answer: t(9;22)(q34;q11)

t(9;22) fuses BCR and ABL1, producing the Philadelphia chromosome in CML and some ALL.

APL with t(15;17) produces the PML-RARA fusion, which is clinically important because it predicts response to:

Answer: All-trans retinoic acid (ATRA)

The PML-RARA fusion sensitizes acute promyelocytic leukemia cells to differentiation therapy with ATRA.

Which quality metric is used to assess overall sequencing accuracy of a base call?

Answer: Phred quality (Q) score

The Phred Q score logarithmically relates to the probability of an incorrect base call, e.g., Q30 = 1 in 1000 error.

A variant found in a healthy population at 5% allele frequency in gnomAD is best classified using which ACMG criterion?

Answer: Stand-alone benign (BA1) for high population frequency

BA1 applies when allele frequency exceeds a threshold (commonly 5%) too high for a pathogenic Mendelian variant.

Which specimen issue most commonly compromises molecular testing of FFPE tissue?

Answer: DNA fragmentation and crosslinking from fixation

Formalin fixation fragments and crosslinks nucleic acids, reducing amplifiable template quality.

IDH1/IDH2 mutation testing in gliomas is important because it:

Answer: Refines classification and confers better prognosis

IDH mutations define a distinct, generally more favorable glioma category in WHO classification.

Sensitivity of an assay to detect a mutation present at low tumor fraction is best described as its:

Answer: Limit of detection

The limit of detection defines the lowest variant allele fraction the assay can reliably identify.