Germline cancer risk conditions are recognised increasingly as drivers of haematopoietic malignancies (HMs). Our group has defined the frequency with which deleterious germline variants are found in HM patients. 1,2 The causative gene varies with the presenting age. For those with myelodysplastic syndrome (MDS)/aplastic anaemia (AA), genes encoding transcriptional regulators are common in children, DNA repair and telomere biology genes dominate throughout adulthood, and DDX41 is seen in the elderly. We see a similar phenomenon for patients with multiple myeloma, with KDM1A prominent in young people and BRCA2 , CHEK2 , and ATM in older adults. 3 Deleterious germline DDX41 variants drive HMs with unique pathogenesis. Among pedigrees with HMs and solid tumours, many test positive for second inherited cancer risk factors, raising the possibility that DDX41 alleles could modify solid tumour development. Allogeneic transplantation (alloTx) continues to present unique challenges. Currently, donors are not screened routinely for germline risk, and the relatively high population frequencies of some cancer risk alleles result in them being introduced inadvertently into the alloTx recipient. Consensus in the alloTx community is needed regarding when data warrant inclusion of germline predisposition testing as an element of standard pre-Tx work-up for both patient/alloTx recipient and donor.
Lucy A. Godley (Sun,) studied this question.