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Study Description

The pathogenesis of chronic lymphocytic leukemia (CLL), the most common leukemia in adults, is still largely unknown since the full spectrum of genetic lesions that are present in the CLL genome, and therefore the number and identity of dysregulated cellular pathways, have not been identified. By combining next-generation sequencing and copy number analysis, we show here that the typical CLL coding genome contains less than 20 clonally represented gene alterations/case, including predominantly non-silent mutations and fewer copy number aberrations. These analyses led to the discovery of several genes not previously known to be altered in CLL. While most of these genes were affected at low frequency in an expanded CLL screening cohort, mutational activation of NOTCH1, observed in 8.3% of CLL at diagnosis, was detected at significantly higher frequency during disease progression toward Richter transformation (31.0%) as well as in chemorefractory CLL (20.8%). Consistent with the association of NOTCH1 mutations with clinically aggressive forms of the disease, NOTCH1 activation at CLL diagnosis emerged as an independent predictor of poor survival. These results provide initial data on the complexity of the CLL coding genome and identify a dysregulated pathway of diagnostic and therapeutic relevance.

  • Study Types: Exome Sequencing, Tumor vs. Matched-Normal
  • Number of study subjects that have individual level data available through Authorized Access: 5

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

1. Previously untreated, diagnoses of Chronic Lymphocytic Leukemia
2. For the whole exome sequencing study, matched tumor and normal genomic DNA

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Genotyping Affymetrix AFFY_6.0 934940 52074
Whole Exome Sequencing Roche 454 GS FLX Titanium N/A N/A
Exome Capture Roche High Density 2.1M Human Exome Array N/A N/A
Selected publications
Diseases/Traits Related to Study (MESH terms)
Authorized Data Access Requests
Study Attribution
  • Principal Investigators
    • Riccardo Dalla-Favera. Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA
    • Laura Pasqualucci. Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, USA
  • Funding Source
    • RO1 CA-37295. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA