Novel recurrent chromosome anomalies in Shwachman–Diamond syndrome

Abstract

Some of the newly recognized clonal anomalies in BM reported here are recurrent, especially unbalanced structural anomalies of chromosome 7, a further complex rearrangement of the del(20)(q) with duplicated and deleted portions, and an unbalanced translocation t(3;6), with partial trisomy of the long arm of chromosome 3 and partial monosomy of the long arm of chromosome 6. Firm conclusions on the possible prognostic relevance of these anomalies would require further study with larger patient cohorts, but our data are sufficient to suggest that these patients necessitate more frequent cytogenetic monitoring. The results on anomalies found in single cells confirm the presence of an SDS-specific karyotype instability.

Shwachman‐Diamond syndrome with clonal interstitial deletion of the long arm of chromosome 20 in bone marrow: haematological features, prognosis and genomic instability

“… Patient also had a subclone with a rearrangement of the del(20)(q), with deleted and duplicated portions of chromosome 20 (Valli et al , ). …”

“…We also reported evidence that several different cell lines, with different chromosome changes, can be found in BM of SDS patients (Pressato et al , ). This is case when the i(7)(q10) and the del(20)(q) are acquired subsequently in different clones, or clones with further rearrangements of del(20)(q), or together with i(7)(q10) or del(20)(q), other different anomalies in independent clones (Pressato et al , ; Valli et al , ).…”

“…Recurring gains, losses (A) and copy number neutral loss of heterozygosity (B), found in ≥2 patients, derived from single nucleotide polymorphism-array analysis of 14 patients (Table I) *Patient also had an independent clone with i(7)(q10). †Patient also had a subclone with a rearrangement of the del(20)(q), with deleted and duplicated portions of chromosome 20 (Valli et al, 2017b). ‡Mild: neutrophil count 0Á5-1Á5 9 10 9 /l, severe <0Á5 9 10 9 /l.…”

“…We also reported evidence that several different cell lines, with different chromosome changes, can be found in BM of SDS patients (Pressato et al, 2015). This is case when the i(7)(q10) and the del(20)(q) are acquired subsequently in different clones, or clones with further rearrangements of del (20)(q), or together with i(7)(q10) or del(20)(q), other different anomalies in independent clones (Pressato et al, 2015;Valli et al, 2017b). Table IV provides some basic information about the haematological condition of our patients with del(20)(q) at the time of a-CGH analysis, the criteria used to consider the level of severity of the condition, together with their age and proportion of BM cells bearing the del(20)(q).…”

Cellular and molecular architecture of hematopoietic stem cells and progenitors in genetic models of bone marrow failure

“…There is also evidence for short telomeres and genomic instability in SDS (42,43). These pathologies may lead to somatic structural chromosomal abnormalities that are commonly seen in SDS (37,43,44) and in FA (45,46); however, they may not directly explain the increased numbers of SNVs seen in our study. In FA, DNA interstrand cross-links may lead to DNA double-strand breaks due to prolonged stalling of the replication fork or collapse.…”