ID

45742

Description

Principal Investigator: Michael Dean, PhD, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA MeSH: Leukemia, Lymphocytic, Chronic, B-Cell https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001181 Chronic lymphocytic leukemia (CLL) is a frequent B-cell malignancy characterized by recurrent somatic chromosome alterations and a low level of point mutations. Here we present single nucleotide polymorphism (SNP) microarray analyses of a single CLL patient over 29-years of observation and treatment, and transcriptome and whole genome sequencing at selected timepoints. We identified chromosome alterations of 13q14-, 6q- and 12q+ in early cell clones, elimination of clonal populations following therapy, and subsequent appearance of a clone containing trisomy 12 and a chromosome 10 copy neutral loss of heterogeneity (LOH) that marks a major population dominant at death. Serial single cell RNA sequencing revealed elevated mRNA expression of the FOS, JUN and KLF4 genes just before the appearance of acute disease requiring therapy. This gene expression pattern became undetectable following therapy, but reoccurred following relapse. Transcriptome evolution indicates that complex expression changes occur over time. In conclusion, CLL can evolve gradually during indolent phases, and undergo rapid changes following therapy.

Link

dbGaP-study=phs001181

Keywords

  1. 6/2/23 6/2/23 - Chiara Middel
Copyright Holder

Michael Dean, PhD, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Uploaded on

June 2, 2023

DOI

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License

Creative Commons BY 4.0

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    dbGaP phs001181 Single-Cell DNA and RNA Sequencing over A 29-Year Period of A CLL Patient

    This data table contains a mapping of study subject IDs to sample IDs. Samples are the final preps submitted for genotyping, sequencing, and/or expression data. For example, if one patient (subject ID) gave one sample, and that sample was processed differently to generate 2 sequencing runs, there would be two rows, both using the same subject ID, but having 2 unique sample IDs. The data table also includes sample use.

    pht005770
    Description

    pht005770

    Alias
    UMLS CUI [1,1]
    C3846158
    De-identified Subject ID
    Description

    SUBJECT_ID

    Data type

    string

    Alias
    UMLS CUI [1,1]
    C4684638
    UMLS CUI [1,2]
    C2348585
    De-identified Sample ID
    Description

    SAMPLE_ID

    Data type

    string

    Alias
    UMLS CUI [1,1]
    C4684638
    UMLS CUI [1,2]
    C1299222
    Sample use. Array_SNP: SNP genotypes obtained using standard or custom microarrays; Seq_DNA_WholeGenome: Whole transcriptome sequencing; Seq_RNA: Whole genome sequencing
    Description

    SAMPLE_USE

    Data type

    string

    Alias
    UMLS CUI [1,1]
    C2347026
    UMLS CUI [1,2]
    C1524063

    Similar models

    This data table contains a mapping of study subject IDs to sample IDs. Samples are the final preps submitted for genotyping, sequencing, and/or expression data. For example, if one patient (subject ID) gave one sample, and that sample was processed differently to generate 2 sequencing runs, there would be two rows, both using the same subject ID, but having 2 unique sample IDs. The data table also includes sample use.

    Name
    Type
    Description | Question | Decode (Coded Value)
    Data type
    Alias
    Item Group
    pht005770
    C3846158 (UMLS CUI [1,1])
    SUBJECT_ID
    Item
    De-identified Subject ID
    string
    C4684638 (UMLS CUI [1,1])
    C2348585 (UMLS CUI [1,2])
    SAMPLE_ID
    Item
    De-identified Sample ID
    string
    C4684638 (UMLS CUI [1,1])
    C1299222 (UMLS CUI [1,2])
    SAMPLE_USE
    Item
    Sample use. Array_SNP: SNP genotypes obtained using standard or custom microarrays; Seq_DNA_WholeGenome: Whole transcriptome sequencing; Seq_RNA: Whole genome sequencing
    string
    C2347026 (UMLS CUI [1,1])
    C1524063 (UMLS CUI [1,2])

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