Free MGP Practice Questions

Question 1

An invasive breast carcinoma has HER2 immunohistochemistry scored 2+. Dual-probe ISH on the same block shows a HER2/CEP17 ratio of 2.4 and a mean of 3.3 HER2 signals per cell. A second observer, blinded to the first count, evaluates 30 additional invasive tumor cells in the corresponding area and obtains a ratio of 2.3 with 3.5 HER2 signals per cell. Controls are satisfactory, with no distinct amplified population or histopathologic discordance. Under the ASCO/CAP interpretation algorithm, how should HER2 status be finalized?

Accepted Answer

Negative for HER2 overexpression/amplification, with the explanatory comment.

Answer

Positive for HER2 amplification because both HER2/CEP17 ratios exceed 2.0.

Answer

Equivocal, requiring another tumor block before any final status can be assigned.

Answer

Indeterminate, requiring an alternative chromosome 17 probe to resolve the ratio.

Question 2

A 68-year-old man develops progressive intention tremor and gait ataxia. He had normal childhood development. FMR1 testing identifies an unmethylated allele containing 93 CGG repeats. Which interpretation connects the molecular result with his presentation?

Accepted Answer

A premutation associated with fragile X-associated tremor/ataxia syndrome.

Answer

An intermediate allele associated only with reproductive instability.

Answer

A full mutation causing classic fragile X syndrome through FMR1 silencing.

Answer

A normal-range allele that redirects the evaluation toward unrelated ataxias.

Question 3

The on-call pathologist reviews blood from a 31-year-old patient with gingival bleeding and extensive bruising. Platelets are 18 × 10^9/L, fibrinogen is 70 mg/dL, and numerous abnormal promyelocytes contain bundles of Auer rods. Coagulopathy support has begun, but rapid PML::RARA testing is not yet complete. The treating physician asks whether all-trans retinoic acid should await the result. What is the appropriate recommendation?

Accepted Answer

Begin all-trans retinoic acid now and expedite PML::RARA confirmation.

Answer

Normalize fibrinogen before beginning all-trans retinoic acid.

Answer

Wait for PML::RARA confirmation before exposing the patient to all-trans retinoic acid.

Answer

Complete the broad AML molecular panel before selecting a differentiation-based treatment.

Question 4

DNA sequencing of a lung adenocarcinoma detects an intronic MET variant near exon 14, but its effect on splicing is uncertain. Adequate, well-preserved tumor RNA is available. The remaining question is whether the tumor expresses a transcript that omits exon 14. Which experiment answers that question most directly?

Accepted Answer

Reverse-transcription PCR across exons 13-15, followed by amplicon sequencing.

Answer

Genomic Sanger sequencing of exon 14 and both adjacent splice junctions.

Answer

Dual-color MET/CEP7 FISH, with enumeration of signals in invasive tumor nuclei.

Answer

MLPA using separate dosage probes for MET exons 13, 14, and 15.

Question 5

A woman is a confirmed carrier of a CF-causing CFTR variant. Her clinically unaffected partner has a full sibling with cystic fibrosis; his unaffected parents are obligate carriers. The sibling’s molecular results are unavailable. His carrier panel is negative. For this family, assume the panel detects 90% of carriers, has 100% specificity, and the recessive disease is fully penetrant. Assuming disease-causing variants from the two partners would cause cystic fibrosis when inherited together, what is the residual risk of an affected child per pregnancy?

Accepted Answer

1 in 24.

Answer

1 in 6.

Answer

1 in 44.

Answer

1 in 60.

Question 6

In a qualitative multiplex PCR assay, a patient specimen produces a strong, reproducible target signal at Cq 18, while its internal amplification control is undetected. Extraction blanks and no-template controls are negative; the positive control and other specimens’ internal controls perform as expected. Validation demonstrated that target concentrations in this range can suppress the internal control through competition without compromising a positive call. How should this specimen be handled?

Accepted Answer

Report the target as detected under the validated interpretation rules.

Answer

Re-extract the specimen and withhold its result until the internal control amplifies.

Answer

Invalidate the run because a patient internal control failed.

Answer

Report an inconclusive result and require confirmation by an unrelated method.

Question 7

A 39-year-old patient’s colorectal carcinoma shows loss of MSH2 and MSH6, with retained MLH1 and PMS2 and intact internal staining controls. Germline sequencing and deletion/duplication analysis of MSH2 and MSH6 are negative. The hereditary-cancer evaluation is being expanded rather than treating the tumor’s staining pattern as proof of Lynch syndrome. Which additional germline finding would provide a mechanism for this paired protein loss?

Accepted Answer

A 3′ EPCAM deletion causing methylation and silencing of adjacent MSH2.

Answer

Biallelic MUTYH variants causing failure of base-excision repair.

Answer

An APC promoter 1B variant causing gastric polyposis predisposition.

Answer

An MLH1 deletion causing destabilization of its mismatch-repair partner.

Question 8

A colorectal biopsy contains 12% tumor nuclei after the best feasible enrichment. Tumor and background cells are diploid at KRAS. The laboratory is considering whether its negative result can exclude a KRAS variant that, if present, would be heterozygous in every tumor cell and absent from non-neoplastic cells. The assay reliably detects variants at or above 10% variant allele fraction. Which assessment of this negative result is justified?

Accepted Answer

The expected variant allele fraction is 6%; the negative result cannot reliably exclude the variant.

Answer

The expected variant allele fraction is 12%; the negative result reliably excludes the variant.

Answer

The expected variant allele fraction is 24%; the negative result reliably excludes the variant.

Answer

The expected variant allele fraction is 50%; the negative result reliably excludes the variant.

Question 9

A kidney transplant recipient has rising plasma CMV DNA despite appropriately dosed intravenous ganciclovir. Resistance testing detects a recognized ganciclovir-resistance substitution in UL97, with no resistance-associated alteration detected in UL54. Which step in drug action is most directly impaired by the UL97 finding?

Accepted Answer

Initial phosphorylation of ganciclovir by the viral protein kinase.

Answer

Binding of ganciclovir triphosphate to the viral DNA polymerase.

Answer

Host-kinase conversion of ganciclovir monophosphate to triphosphate.

Answer

Retention of incorporated ganciclovir during proofreading by the viral DNA polymerase.

Question 10

Following percutaneous coronary intervention for an acute coronary syndrome, a patient’s CYP2C19 result is *2/*17. The laboratory identifies *2 as a no-function allele and *17 as an increased-function allele. There is no contraindication to ticagrelor. Which genotype-to-phenotype interpretation and prescribing recommendation is supported by CPIC guidance?

Accepted Answer

Intermediate metabolizer; use ticagrelor rather than standard-dose clopidogrel.

Answer

Normal metabolizer; use standard-dose clopidogrel.

Answer

Rapid metabolizer; reduce the clopidogrel dose to compensate for increased activation.

Answer

Intermediate metabolizer; retain clopidogrel and routinely double its maintenance dose.

Free MGP Practice Questions

Domain 2: Molecular Genetic Principles 7% of exam

Question 1

Domain 3: Techniques and Methods 5% of exam

Question 2

Domain 4: Assay Performance and Validation 7% of exam

Question 3

Domain 5: Quality 6% of exam

Question 4

Domain 8: Inherited Diseases 10% of exam

Question 5

Domain 9: Inherited cancer Syndromes 5% of exam

Question 6

Domain 10: Solid Tumors 11% of exam

Question 7

Domain 11: Hematopathology 9% of exam

Question 8

Domain 12: Pharmacogenetics 5% of exam

Question 9

Domain 13: Infectious Disease 6% of exam

Question 10

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