Molecular Genetic Pathology Flashcards

The JAK2 V617F mutation is a key diagnostic marker for which group of disorders?

Answer: Myeloproliferative neoplasms

JAK2 V617F is present in most polycythemia vera cases and many essential thrombocythemia and primary myelofibrosis cases.

Which molecular finding defines a favorable-risk category in acute myeloid leukemia when NPM1 is mutated?

Answer: NPM1 mutation without FLT3-ITD (or low allelic ratio)

NPM1 mutation in the absence of FLT3-ITD (or with a low ratio) confers favorable prognosis in AML.

Pharmacogenomic testing of TPMT is performed primarily to guide dosing of:

Answer: Thiopurine drugs such as azathioprine and 6-mercaptopurine

TPMT activity affects thiopurine metabolism; deficient patients risk severe myelosuppression at standard doses.

A synonymous variant classified per ACMG/AMP guidelines is generally considered which criterion supporting benign impact?

Answer: No predicted effect on protein sequence or splicing (BP7)

BP7 applies to synonymous changes with no predicted splicing impact and no conservation of the nucleotide.

Bisulfite conversion is a required step for which type of analysis?

Answer: DNA methylation detection

Bisulfite converts unmethylated cytosines to uracil while methylated cytosines are protected, enabling methylation analysis.

The BRAF V600E mutation is targeted by vemurafenib and is most characteristically found in:

Answer: Melanoma

BRAF V600E is common in melanoma and predicts response to BRAF inhibitors like vemurafenib.

Clonality assessment of a suspected B-cell lymphoma is best performed by evaluating:

Answer: Immunoglobulin heavy chain (IGH) gene rearrangement

PCR-based IGH rearrangement analysis detects clonal B-cell populations supporting a lymphoma diagnosis.