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Series GSE227690 Query DataSets for GSE227690
Status Public on Mar 27, 2023
Title Ultraviolet radiation shapes dendritic cell leukaemia transformation in the skin
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Other
Summary Tumours most often arise from progression of precursor clones within a single anatomical niche. In the bone marrow, clonal progenitors can undergo malignant transformation to acute leukaemia, or differentiate into immune cells that contribute to disease pathology in peripheral tissues. Outside the marrow, these clones are potentially exposed to a variety of tissue-specific mutational processes, although the consequences of this are unclear. Here we investigate the development of blastic plasmacytoid dendritic cell neoplasm (BPDCN)-an unusual form of acute leukaemia that often presents with malignant cells isolated to the skin. Using tumour phylogenomics and single-cell transcriptomics with genotyping, we find that BPDCN arises from clonal (premalignant) haematopoietic precursors in the bone marrow. We observe that BPDCN skin tumours first develop at sun-exposed anatomical sites and are distinguished by clonally expanded mutations induced by ultraviolet (UV) radiation. A reconstruction of tumour phylogenies reveals that UV damage can precede the acquisition of alterations associated with malignant transformation, implicating sun exposure of plasmacytoid dendritic cells or committed precursors during BPDCN pathogenesis. Functionally, we find that loss-of-function mutations in Tet2, the most common premalignant alteration in BPDCN, confer resistance to UV-induced cell death in plasmacytoid, but not conventional, dendritic cells, suggesting a context-dependent tumour-suppressive role for TET2. These findings demonstrate how tissue-specific environmental exposures at distant anatomical sites can shape the evolution of premalignant clones to disseminated cancer.
 
Overall design This GEO repository contains single-cell sequencing data on the bone marrow of six healthy donors, five BPDCN patients without overt bone marrow involvement, and six BPDCN patients with bone marrow involvement. Whole genome and whole exome sequencing data for this study can be found on dbGaP.
Web link https://www.ncbi.nlm.nih.gov/pubmed/37286599
 
Contributor(s) Griffin GK, Booth CA, Togami K, Chung SS, Ssozi D, Verga JA, Bouyssou JM, Lee YS, Shanmugam V, Hornick JL, LeBoeuf NR, Morgan EA, Bernstein BE, Hovestadt V, van Galen P, Lane AA
Citation(s) 37286599
Submission date Mar 20, 2023
Last update date Jun 26, 2023
Contact name Peter van Galen
E-mail(s) petervangalen@gmail.com, pvangalen@bwh.harvard.edu
Organization name Brigham and Women's Hospital / Broad Institute of MIT and Harvard
Department Hematology
Lab Van Galen Lab
Street address 4 Blackfan Circle
City Boston
State/province Massachusetts
ZIP/Postal code 02115
Country USA
 
Platforms (2)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (111)
GSM7105550 BM1_BioRep1_scRNAseq
GSM7105551 BM1_BioRep2_scRNAseq
GSM7105552 BM1_BioRep3_scRNAseq
Relations
BioProject PRJNA946651

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE227690_BM_counts.tsv.gz 44.8 Mb (ftp)(http) TSV
GSE227690_BM_metadata.tsv.gz 1.1 Mb (ftp)(http) TSV
GSE227690_BM_norm.tsv.gz 91.6 Mb (ftp)(http) TSV
GSE227690_Pt10Dx_counts.tsv.gz 15.8 Mb (ftp)(http) TSV
GSE227690_Pt10Dx_metadata.tsv.gz 345.4 Kb (ftp)(http) TSV
GSE227690_Pt10Dx_norm.tsv.gz 27.6 Mb (ftp)(http) TSV
GSE227690_Pt10Rel_counts.tsv.gz 9.7 Mb (ftp)(http) TSV
GSE227690_Pt10Rel_metadata.tsv.gz 196.6 Kb (ftp)(http) TSV
GSE227690_Pt10Rel_norm.tsv.gz 21.3 Mb (ftp)(http) TSV
GSE227690_Pt12Dx_counts.tsv.gz 8.4 Mb (ftp)(http) TSV
GSE227690_Pt12Dx_metadata.tsv.gz 217.2 Kb (ftp)(http) TSV
GSE227690_Pt12Dx_norm.tsv.gz 19.7 Mb (ftp)(http) TSV
GSE227690_Pt12Rel_counts.tsv.gz 5.0 Mb (ftp)(http) TSV
GSE227690_Pt12Rel_metadata.tsv.gz 161.0 Kb (ftp)(http) TSV
GSE227690_Pt12Rel_norm.tsv.gz 12.5 Mb (ftp)(http) TSV
GSE227690_Pt14Dx_counts.tsv.gz 9.0 Mb (ftp)(http) TSV
GSE227690_Pt14Dx_metadata.tsv.gz 226.4 Kb (ftp)(http) TSV
GSE227690_Pt14Dx_norm.tsv.gz 20.2 Mb (ftp)(http) TSV
GSE227690_Pt15Dx_counts.tsv.gz 5.2 Mb (ftp)(http) TSV
GSE227690_Pt15Dx_metadata.tsv.gz 70.6 Kb (ftp)(http) TSV
GSE227690_Pt15Dx_norm.tsv.gz 4.5 Mb (ftp)(http) TSV
GSE227690_Pt16Dx_counts.tsv.gz 4.1 Mb (ftp)(http) TSV
GSE227690_Pt16Dx_metadata.tsv.gz 86.9 Kb (ftp)(http) TSV
GSE227690_Pt16Dx_norm.tsv.gz 11.3 Mb (ftp)(http) TSV
GSE227690_Pt1Dx_counts.tsv.gz 2.3 Mb (ftp)(http) TSV
GSE227690_Pt1Dx_metadata.tsv.gz 81.0 Kb (ftp)(http) TSV
GSE227690_Pt1Dx_norm.tsv.gz 5.5 Mb (ftp)(http) TSV
GSE227690_Pt1Rem_counts.tsv.gz 12.9 Mb (ftp)(http) TSV
GSE227690_Pt1Rem_metadata.tsv.gz 322.1 Kb (ftp)(http) TSV
GSE227690_Pt1Rem_norm.tsv.gz 28.1 Mb (ftp)(http) TSV
GSE227690_Pt5Dx_counts.tsv.gz 4.7 Mb (ftp)(http) TSV
GSE227690_Pt5Dx_metadata.tsv.gz 133.5 Kb (ftp)(http) TSV
GSE227690_Pt5Dx_norm.tsv.gz 11.1 Mb (ftp)(http) TSV
GSE227690_Pt9Dx_counts.tsv.gz 6.7 Mb (ftp)(http) TSV
GSE227690_Pt9Dx_metadata.tsv.gz 132.1 Kb (ftp)(http) TSV
GSE227690_Pt9Dx_norm.tsv.gz 15.6 Mb (ftp)(http) TSV
GSE227690_RAW.tar 540.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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