Clonal evolution in relapsed acute myeloid leukemia revealed by whole genome sequencing

By Li Ding, T. Ley, David E. Larson, Christopher A. Miller, Daniel C. Koboldt, J. Welch, Julie Ritchey, Margaret A. Young, T. Lamprecht, M. McLellan and 29 more. Nature, 2012

2,069 citations recorded by the source corpus.

Most patients with acute myeloid leukaemia (AML) die from progressive disease after relapse, which is associated with clonal evolution at the cytogenetic level. To determine the mutational spectrum associated with relapse, we sequenced the primary tumour and relapse genomes from eight AML patients, and validated hundreds of somatic mutations using deep sequencing; this allowed us to define clonality and clonal evolution patterns precisely at relapse. In addition to discovering novel, recurrently mutated genes (for example, WAC, SMC3, DIS3, DDX41 and DAXX) in AML, we also found two major clonal evolution patterns during AML relapse: (1) the founding clone in the primary tumour gained mutations and evolved into the relapse clone, or (2) a subclone of the founding clone survived initial therapy, gained additional mutations and expanded at relapse. In all cases, chemotherapy failed to eradicate the founding clone. The comparison of relapse-specific versus primary tumour mutations in all eight cases revealed an increase in transversions, probably due to DNA damage caused by cytotoxic chemotherapy. These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped, in part, by the chemotherapy that the patients receive to establish and maintain remissions.

Subfields: Cancer Research, Hematology

View Paper: https://www.semanticscholar.org/paper/2bdfc064e97f063a991d04d3de622ffc59e13807

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Citations in the corpus

Mutational Analysis Reveals the Origin and Therapy-driven Evolution of Recurrent Glioma (2013, neutral): “In contrast to the clonal evolution of hematological malignancies (3, 4) and solid tumor metastases (5-7), the local regrowth of solid tumors after surgery occurs under a unique set of evolutionary pressures, which are further impacted by adjuvant therapies.”
Cancer therapy shapes the fitness landscape of clonal hematopoiesis (2020, neutral): “The distribution of CH VAF, number of mutations, CH gene and peripheral blood count indexes using our cohort of MSK solid tumor cancer patients aged 50–75 who were untreated prior to blood draw; 6.”
The Life History of 21 Breast Cancers (2012, background): “…however, cancers are recognized to be mixtures of competing subclones, based on analyses of cancers sampled within a patient at different times (Ding et al., 2012; Shah et al., 2009), from different sites (Campbell et al., 2010; Ding et al., 2010; Yachida et al., 2010), at hypermutable genomic…”
Evolution and impact of subclonal mutations in chronic lymphocytic leukemia (2013, methodology): “This finding demonstrates that coexisting sibling subclones are at least as common in CLL as are linear nested subclones, as demonstrated in other hemato- logical malignancies (Ding et al., 2012; Egan et al., 2012).”
Absolute quantification of somatic DNA alterations in human cancer (2012, background): “MPD (205) GIST (36) Lung adeno (543) Esophageal squamous (32) Lung squamous (46) Breast cancer (134) Liposarcoma (93) Other sarcoma (66) Esophageal adeno (69) Prostate cancer (61) Ovarian cancer (90) MFH (36) ALL (235) Medulloblastoma (96) Colorectal cancer (125) HCC (108) Cell lines (364) Neuroblas”