Myeloid neoplasms with germline predisposition: Practical considerations and complications in the search for new...

Genomic research in hematological malignancies has focused far more prominently on somatic mutations than on germline variants. Although increasing numbers of germline variants are being identified, a substantial proportion of familial myeloid malignancies have no causal allele pinpointed. Here we review the biological, technological, and clinical challenges that stand in the way of the goal of establishing, implementing, and interpreting a comprehensive panel of germline variants for testing. Achieving this goal would inform care for large numbers of myeloid malignancy patients. Furthermore, knowledge of germline susceptibility variants and their corresponding genes will shed light on disease processes, potentially suggesting therapeutic strategies tailored to specific variants.