Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features
Menée à partir d'échantillons de cellules mononucléées du sang périphérique et d'échantillons salivaires prélevés sur des patients atteints d'une leucémie lymphoïde chronique, cette étude identifie 186 altérations génétiques permettant de définir cinq sous-groupes génomiques associés à la réponse thérapeutique
The value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom’s 100,000 Genomes Project. We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity. We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. While requiring independent validation, our findings highlight the potential of whole-genome sequencing to inform future risk stratification in chronic lymphocytic leukemia.
Nature Genetics , article en libre accès, 2022