High density copy number analysis and whole exome sequencing of unselected chronic lymphocytic leukemia cases and of paired chronic lymphocytic leukemia and Richter Syndrome cases

Study ID Alternative Stable ID Type
phs000364 Tumor vs. Matched-Normal

Study Description

Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation

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 ... (Show More)

Archive Link Archive Accession
dbGaP phs000364

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