Genetic predisposition to leukemia and other hematologic malignancies

How I curate: applying American Society of Hematology-Clinical Genome Resource Myeloid Malignancy Variant Curation Expert Panel rules for RUNX1 variant curation for germline predisposition to myeloid malignancies

“…Here, in keeping with our MM-VCEP rules, cultured skin fibroblasts (gold standard, albeit invasive, costly, and time-consuming), cultured bone marrow mesenchymal stromal cells or DNA from hair roots are appropriate sources. 59,60 Alternatively, confirmation of the germline nature of a variant can be achieved by demonstrating its presence in two or more related individuals. The possibility of sample contamination by malignant cells is significant and consequently, peripheral blood, bone marrow, saliva, buccal swabs, DNA from paraffin blocks and even fingernails, which can contain monocytes, are inappropriate samples for germline testing.…”

Do next-generation sequencing results drive diagnostic and therapeutic decisions in MDS?

“…Over the past decade, we have gained novel insights into the genetic origin of inherited myeloid malignancies. 36,37 Mutations in GATA2, RUNX1, DDX41, and ETV6 are examples of germline mutations associated with MDS and AML. 36,37 The detection of germline mutations has a significant impact not only for treatment decisions but also for the patient's family.…”

Germline ETV6 mutations and predisposition to hematological malignancies

“…Genetic counseling and site-specific testing should be offered to any at-risk family member. Matched-related stem cell donors should be considered very carefully, and donors with known germline mutation or unclear carrier status should be avoided [41,42].…”