ID
45217
Description
Principal Investigator: Catherine Wu, Broad Institute, Cambridge, MA, Dana Farber Cancer Institute, Boston MA, USA MeSH: Chronic Lymphocytic Leukemia,Leukemia, Lymphocytic, Chronic, B-Cell https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000435 The somatic genetic basis of chronic lymphocytic leukemia (CLL), a common and clinically heterogenous adult leukemia, remains poorly understood. Massively parallel sequencing technology now provides a method for systematic discovery of genetic alterations that underlie disease, and for uncovering new therapeutic targets and biomarkers. In study version 2 we presented a dataset consisting of DNA sequencing from 169 CLL samples (with matched germline controls). Samples were collected from patients displaying a wide range of characteristics representing the broad clinical spectrum of CLL. Understanding the mutational landscape of CLL provides a starting point for systematic analyses to address fundamental questions in CLL, including how mutated genes alter cellular networks and phenotypes, and thereby contribute to disease heterogeneity. Intratumoral heterogeneity plays a critical role in tumor evolution. To define the contribution of DNA methylation to heterogeneity within tumors, we performed genome-scale bisulfite sequencing of 100 primary chronic lymphocytic leukemias (CLLs; data presented in study version 3). Compared with 26 normal B cell samples, CLLs consistently displayed higher intrasample variability of DNA methylation patterns across the genome, which appears to arise from stochastically disordered methylation in malignant cells. Transcriptome analysis of bulk and single CLL cells revealed that methylationdisorder was linked to low-level expression. Disordered methylation was further associated with adverse clinical outcome. We therefore propose that disordered methylation plays a similar role to that of genetic instability, enhancing the ability of cancer cells to search for superior evolutionary trajectories.
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Versions (2)
- 7/31/22 7/31/22 - Chiara Middel
- 10/12/22 10/12/22 - Adrian Schulz
Copyright Holder
Catherine Wu, Broad Institute, Cambridge, MA, Dana Farber Cancer Institute, Boston MA, USA
Uploaded on
October 12, 2022
DOI
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License
Creative Commons BY 4.0
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dbGaP phs000435 Whole Exome Sequencing of Chronic Lymphocytic Leukemia
Subject - Sample Mapping
- StudyEvent: SEV1
- Subject - Consent - Affection Status Information
- Subject - Sample Mapping
- The dataset contains molecular phenotype data, e.g. status of IGHV (mutated/unmutated), ZAP70, trisomy 12, deletions on chromosomes 11, 13 and 17 (negative/positive), and basic sociodemographic information, i.e. age, gender and ethnicity of n=186 subjects.
- The dataset contains information about sample and tumor type (tumor/normal; primary/not).
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Subject - Sample Mapping
- StudyEvent: SEV1
- Subject - Consent - Affection Status Information
- Subject - Sample Mapping
- The dataset contains molecular phenotype data, e.g. status of IGHV (mutated/unmutated), ZAP70, trisomy 12, deletions on chromosomes 11, 13 and 17 (negative/positive), and basic sociodemographic information, i.e. age, gender and ethnicity of n=186 subjects.
- The dataset contains information about sample and tumor type (tumor/normal; primary/not).
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