In this week's Nature, two separate research teams publish studies characterizing the genomics of childhood cancers. In the first study, a multi-institute group presents a comprehensive analysis of genetic alterations in 961 tumors from young people with 24 distinct molecular types of cancer, uncovering mutations in genes involved in double-stranded DNA break repair across all cancers. Notably, the scientists also found that nearly half of the tumors studied contained mutations targeted by existing drugs or ones currently under development.
In the second paper, a St. Jude Children's Research Hospital-led team reports a genomic and transcriptomic analysis of nearly 1,700 pediatric leukemias and solid tumors. Among the findings are 42 cancer associated genes — of which only 45 percent matched those found in similar studies of adult cancers — and 11 genome-wide mutational signatures, including one attributed to ultraviolet light exposure. Taken together, the studies highlight the druggable nature of many childhood cancers, as well as the need for pediatric-specific precision therapies.
And in Nature Plants, a Seoul National University researcher provides an overview of chemical-based approaches to precision genome editing. In the perspective piece, Jin-Soo Kim discusses base editors that can enable single nucleotide conversions efficiently and reversibly without double-stranded DNA cleavage, and touches on the hurdles that still face their widespread use.
Meanwhile, in Nature Genetics, a multi-institute group of scientists presents a map of sequence constraints for the human genome. The investigators used 11,257 whole-genome sequences and 16,384 heptamers to build the map, which differs substantially from traditional maps of interspecies conservation and identifies regulatory elements among the most constrained regions of the genome. Among their findings was that constrained regions of the noncoding genome are up to 52-fold enriched for known pathogenic variants as compared to unconstrained regions, and that most constrained regulatory elements associate with the most essential genes. "This map of sequence constraint across thousands of individuals is an asset to help interpret noncoding elements in the human genome, prioritize variants, and reconsider gene units at a larger scale," the investigators conclude.
The Daily Scan's sister publication, GenomeWeb Daily News, has more on this study here.