In a paper published online in advance in Nature, researchers at St. Jude Children's Research Hospital, Washington University School of Medicine in St. Louis, and elsewhere report on their whole-genome sequencing of retinoblastomas. "The overall mutational rate was very low; RB1 was the only known cancer gene mutated," the authors write. From there, the team considered a number of non-genetic mechanisms of cancer-related pathway deregulation, eventually finding that "targeting SYK with a small-molecule inhibitor induced retinoblastoma tumor cell death in vitro and in vivo," it reports this week. Overall, the authors suggest that "retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss."
Several researchers from the same St. Jude-WashU team report in a separate Nature paper published online this week on mutations associated with relapse in primary tumor and relapse genomes from eight acute myeloid leukemia patients. "In addition to discovering novel, recurrently mutated genes in AML, we also found two major clonal evolution patterns during AML relapse," the authors write. The researchers found that "the founding clone in the primary tumor gained mutations and evolved into the relapse clone," and that a "subclone of the founding clone survived initial therapy, gained additional mutations and expanded at relapse." Overall, the group says comparing relapse-specific versus primary tumor mutations suggest 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."
In a related article, researchers from St. Jude and WashU report on their whole-genome sequencing of 12 early T-cell precursor acute lymphoblastic leukemia cases, through which they found that "the mutational spectrum is similar to myeloid tumors, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukemia hematopoietic stem cells."
Retraction Watch blog co-creators Adam Marcus and Ivan Oransky discuss post-publication peer review in this week's Nature. The authors say retractions have increased 15-fold during the past decade. Although it's not exactly clear why retractions have risen so much, Marcus and Oransky attribute this trend not to decrease in the overall quality of research, but to heightened vigilance among members of the community to correct the scientific record. The authors also call for changes in scientific publishing that would "make the scientific record more self-correcting."