In tomorrow's issue of Nature, three papers detailing the sequencing of entire human genomes are being published. All of the sequencing reported in the papers was generated using the Illumina/Solexa next-generation sequencing platform. The first paper, Accurate whole human genome sequencing using reversible terminator chemistry, describes the deep sequencing of a YRI (African) HapMap individual by Illumina. The second paper, The diploid genome sequence of an Asian individual, marks the publication of the first Asian individual genome.
The third paper, DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome, details research done at The Genome Center at Washington University in St. Louis on the first whole-genome sequencing of a cancer genome and its matched normal genome. The sequencing was done on tumor and skin samples from a deceased, female patient (it is also the first female genome sequenced) who had acute myeloid leukemia (AML). AML is a very deadly form of leukemia which has not seen much improvement in patient outcome over the last twenty years. This is largely due to the difficulty in finding recurrent, causative mutations that lead to tumorigenesis. Genome-wide studies have not found recurrent large-scale genomic events across a large cohort of AML patients and targeted studies have not found recurrent initiating mutations in the genes they have sequenced. Thus, a non-directed, whole-genome sequencing approach was used in this study in the hope that by avoiding the low-resolution of whole-genome array techniques and the bias of targeted techniques that sequence only previously implicated genes or genomic regions, novel mutations could be found that may unlock the clues needed to better understand the onset of AML. Our approach involved the sequencing of the genomes of both the tumor and normal tissues and then looking for differences between the two. Using this approach we were able to find several mutations in genes never before implicated in AML but whose pathways and involvement in other types of cancer indicates they are promising leads to follow. Further research is being done on those variants and we have started sequencing a second AML patient's tumor and normal genomes. Much more to come.
Due to privacy concerns, the sequencing and mutation data will be made available through a protected access portal at NCBI dbGaP. For more information on the study of cancer through genome sequencing, see Towards a cure for cancer.