Homo sapiens Raw sequence reads

Certain genetic mutations have been recurrently described in pediatric MDS patients through continuous efforts of genome sequencing of the disease, however, their impact on clinical characteristic and prognosis remains a mystery. Here, we analyzed genetic data of 26 pediatric MDS patients, and genetic variations were found in 13 cases (8 RCC, 4 MDS-EB, 1 MDS-EB-t, the latter two types are classified as advanced MDS). In RCC group, transfusion dependency (2/4 vs. 1/4) and disease progression (2/4 vs. 1/4) occurred more frequently in patients with co-occurrence of somatic and germline mutations (CSGMs) than those with somatic mutations alone. CSGMs (4/5 in advanced MDS, 4/8 in RCC), germline pathogenic variants (2/4 in advanced MDS, 1/4 in RCC) and somatic mutations specifically associated with MDS (6/6 in advanced MDS, 8/15 in RCC) were also identified in our study. 3 patients with distinct genetic variations taken as examples in our study presented evidently different clinical outcomes. Case 1 with germline and somatic mutations of unknown significance had a relatively slow disease course and a good prognosis. Case 2 with compound heterozygous germline SBDS variants and somatic mutations such as del20q had a reversed disease outcome and a stable clinical course. Case 3 with a germline GATA2 variant and somatic mutations including -7 had a rapidly progressive course of disease and a worst prognosis. Our findings indicate that genetic background of pediatric MDS is closely linked with disease characteristic as well as outcome and that CSGMs leads to disease progression and poor clinical manifestations. Furthermore, the co-occurrence of germline pathogenic variants and MDS-associated somatic mutations may be relevant to a poor prognosis. It should be emphasized that the interaction between certain germline variants and somatic mutations, such as SBDS and del20q, may result in hematopoietic stem cell adaptation (improve hematopoiesis) and reverse adverse clinical outcomes, which can facilitate the development of targeted therapy.