Different patterns of chromosome 20 interstitial deletion in Shwachman-Diamond syndrome and in myeloid neoplasms

A deletion of the long arms of a chromosome 20, del(20)(q), is recurrent as acquired change in the bone marrow (BM) of patients with acute myeloid leukemia (AML),myelodysplastic syndromes (MDS), andmyeloproliferative neoplasms(MPNs). The fact that this clonal anomaly is frequent also in Shwachman-Diamond syndrome (SDS), led to postulate a link with the risk of SDS patients to develop MDS/AML, evaluated as high as 30%, although some evidence attributes to this anomaly a lower risk, possibly thanks to the loss of the EIF6 gene, mapping in the deleted segment. In patients with MDS/AML/MPNs and del(20)(q), some attempts have been made to establish a common deleted region (CDR) by cytogenetic and molecular genetic methods. The introduction of microarray-based comparative genomic hybridization (a-CGH) was expected to define more precisely one or more CDR, possibly containing genes relevant for the pathogenesis of these diseases. According to the literature,this has not been the case: the size of possible CDRs defined by different authors vary from 100 Kb to 10.2 Mb, with different conclusions. We performed a study by a-CGH in 6 patients affected by SDS and with del(20)(q). We compared the results withthose of one patient of our observation affected by refractory cytopenia, and of 92 patients (56 MDS, 17 AML, 19 MPN)from the literature, allwith del(20)(q) and studied with array techniques. The parallel analysis of all patients\u2019 data showed high variableranges both in proximal and distal breakpointsfor MDS/AML/MPNs patients,in most cases not encompassing theEIF6 gene region.On the contrary,in SDS the pattern of the deletion is more constant and different from MDS/AML/MPNs: in particular, the variability of the proximal breakpoint localization is very tiny, always leading to the loss of EIF6 gene