Using parallel sequencing technologies, Mardis and colleagues have characterized and compared the genomic changes in a biopsy sample from the primary tumour of a patient with basal-like breast cancer and a sample from a cerebellar metastasis that developed 8 months later despite chemotherapy. In addition, the authors sequenced the genome of a blood sample from the patient as a normal control and a xenograft generated using cells from the primary tumour biopsy sample prior to treatment to assess whether the observed changes in mutation frequency were random or therapy-related. They then looked for structural variations, alterations in the copy number of genomic regions and differences in the distribution of mutations among the samples.
Most of the abnormalities observed in the genome of the primary tumour — including 48 point mutations, 28 large deletions, 6 inversions and 7 translocations — were also identified in the xenograft and metastatic tumours, reflecting the unstable genome associated with this type of breast cancer. However, the frequency with which the mutations appeared differed between the samples. Of the 48 mutations detectable in all the tumours, the prevalence of 20 of these was comparable for all three, whereas 26 of them were much more frequent in the xenograft and/or the metastatic tumour. Only two of the mutations found in the three tumours were enriched in the primary tumour.
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