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Donor-derived hematologic malignancies are rare complications of hematopoietic cell transplantation (HCT). Although these are commonly either a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), in general, they are a heterogeneous group of diseases, and a unified mechanism for their development has remained elusive. Here we report next-generation sequencing, including whole-exome sequencing (WES), whole-genome sequencing (WGS), and targeted sequencing, of a case of donor-derived MDS (dMDS) following HCT for high-risk B-lymphoblastic leukemia (B-ALL) in an adolescent. Through interrogation of single-nucleotide polymorphisms (SNPs) in the WGS data, we unequivocally prove that the MDS is donor-derived. Additionally, we sequenced 15 samples from 12 time points, including the initial B-ALL diagnostic sample through several post-HCT remission samples, the dMDS, and representative germline samples from both patient and donor, to show that the MDS-related pathologic mutations, including a canonical ASXL1 (p.Y700*) mutation, were detectable nearly 3 yr prior to the morphological detection of MDS. Furthermore, these MDS mutations were not detectable immediately following, and for >1 yr post-, HCT. These data support the clinical utility of comprehensive sequencing following HCT to detect donor-derived malignancies, while providing insights into the clonal progression of dMDS over a 4-yr period.
Pubmed ID: 29891567
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Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.
View all literature mentionsArchive of aggregated information about sequence variation and its relationship to human health. Provides reports of relationships among human variations and phenotypes along with supporting evidence. Submissions from clinical testing labs, research labs, locus-specific databases, expert panels and professional societies are welcome. Collects reports of variants found in patient samples, assertions made regarding their clinical significance, information about submitter, and other supporting data. Alleles described in submissions are mapped to reference sequences, and reported according to HGVS standard.
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View all literature mentionsOpen source, open access database and literature curation system for community based annotation of experimentally identified DNA regulatory regions, transcription factor binding sites and regulatory variants. Automatically cross referenced against PubMED, Entrez Gene, EnsEMBL, dbSNP, eVOC: Cell type ontology, and Taxonomy database. Community driven resource for curated regulatory annotation.
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