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Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics

Gawad, C., Koh, W., Quake, S.R.

A better understanding of intratumor heterogeneity is required to more fully dissect the events which mediate cancer formation and treatment resistance. We used a novel experimental and computational single-cell sequencing approach to directly measure the clonal structures of childhood ALL samples at diagnosis. This approach enabled us to determine the mutation segregation patterns within a single sample and to reconstruct the tumor’s clonal structures with rigorously validated quantitative analysis. We then identified features of each leukemia sample that were shared across patients, including multiple dominant clonal populations at varied stages in differentiation arrest, clone-specific punctuated cytosine mutagenesis, and the late acquisition of proliferative oncogenic point mutations. Together, these findings provide a high-resolution view of the development of childhood ALL.

Citation

Gawad, C., Koh, W., Quake, S.R. "Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics" Proceedings of the National Academy of Sciences (2014): 17947–52