Week 7: Hereditary hematologic malignancies Flashcards
What are some factors that can complicate family history assessment for cancer?
-Incomplete penetrance
-Mild phenotypes
-Variable expressivity
-De novo cases
List some family history red flags for hereditary heme maligancy?
-AML or MDS before 50yr
-Solid tumors before 50yr
-Childhood cancers
-Low platelet/platelet defects/bleeding concerns
-Bone marrow failure/aplastic anemia
-Hx of BMT
-Premature greying or hair loss
-Easy bruising
-Immunodeficiency
-Hearing loss
-Skeletal anomalies
-Cafe au lait spots
-Heart defects
-Eczema
The more homogenous the diagnoses in a family, the ____ yield of genetic testing? (heme lecture)
Higher!
The more heterogenous the diagnoses in the family, the ___ the yield of genetic testing? (heme lecture)
Lower!
What are some clues in family hx that would indicate a relative had an acute blood cancer?
-Passed away within 5yrs diagnosis
-If they had a BMT
What is a clue that would indicate a relative had a chronic blood cancer?
If they had active surveillance without treatment
What is the standard of care for diagnosing myeloid malignancies?
Molecular/somatic testing
Includes several genes with germline implications
What is a consideration/risk associated with molecular/somatic testing for hematologic malignancies?
Testing can identify germline variants incidentally
T/F Molecular/somatic testing for heme malignancies is insufficient for evaluation of germline variants
True! It is not comprehensive and may not evaluate mutations in all regions, needs further evaluation
What is the most commonly mutated gene in HHM?
DDX41
-Lifetime risk 20-30%
-Moderate penetrance
-Male predominance
-Median age at dx 69yr (difficult to differentiate from sporadic cases)
T/F peripheral blood is not an appropriate sample for analyzing variants for patients with leukemia, MDS, some lymphomas
True!
peripheral blood in these = tumor tissue
This tumor tissue not always useful as it may contain only somatic mutations associated with the cancer
What layer of blood is used for molecular analysis? What types of cells does this layer contain?
Buffy coat!
Contains leukocytes and platelets
T/F Blood/saliva/buccal sample is not an appropriate for presymptomatic relatives of someone with heme malignancy?
False!
What is the gold standard specimens in HHMs?
Skin punch biopsy
Saliva not appropriate because it still collects DNA from same WBC components as blood
What are some scenarios in which blood is not ideal for germline testing?
-Recent transfusion (<4wks)
-Received recent packed cell/platelet transfusion (<2wks)
-Evidence of active hematologic dysplasia (MDS or malignancy)
-Hx of allogenic HSCT
