Whole-Genome Sequencing Improves Cancer Diagnoses
Although whole-
genome sequencing is not yet ready for routine clinical use, two studies show how the approach could improve the diagnosis and, potentially, the treatment of cancer. The reports, in the April 20
Journal of the American Medical Association, describe how researchers at Washington University School of Medicine in St. Louis and their colleagues used whole-genome sequencing to investigate the cases of two patients.
The
first study focused on a 42-year-old woman who died from leukemia that was probably related to previous treatment for
breast and ovarian cancers. The woman did not have a known family history of cancer, and tests for
mutations in the breast cancer-associated genes
BRCA1 and
BRCA2 were negative. But a comparison of the genomes of her cancer cells and normal cells revealed a novel mutation in the
TP53 gene that altered the function of the encoded protein.
TP53 gene mutations have been implicated in a number of cancers, including some early-onset breast and ovarian cancers, as well as
Li-Fraumeni syndrome.
The
TP53 mutation does not appear to have been inherited from one of the patient’s parents. But because the mutation was seen in both normal and cancer cells, it had to have occurred very early in the patient’s life, possibly at conception. Thus, the mutation could have been present in her
germline DNA and been passed on to her children, the researchers noted.
As specified by the study
protocol, the researchers contacted the woman’s primary care physician, who then discussed the issue with the patient’s family members and encouraged them to seek genetic counseling. “Even though the patient died, her contribution to this study yielded new knowledge that might one day save the lives of her children,” study co-author Dan Koboldt of the Genome Institute at Washington University wrote in
a post about the studies on his blog, MassGenomics.
The
second study involved a 39-year-old woman with a form of
acute myeloid leukemia (AML). A comparison of DNA from her tumor and normal cells revealed a fusion of two genes in her blood cells that was not detected through routine
cytogenetic testing. The presence of this gene fusion is associated with good outcomes after chemotherapy. Consequently, the patient’s doctors recommended chemotherapy rather than stem cell transplantation, the treatment that had been indicated by the standard diagnostic testing results.
At the time of publication, the woman had been in remission for 15 months. The sequencing, analysis, and validation of the fusion gene were completed in just 7 weeks, which was quick enough that doctors could use the information to choose the most effective treatment for the patient, the researchers noted.
“These cases of personalized genomic medicine are just some of the first examples of what will likely be commonplace in the near future,” wrote the authors of an accompanying
editorial.
“Clearly, the technology will no longer be the major impediment to widespread clinical use of these tools, and the main challenges will soon move to the clinical implementation and interpretation of genomic data,” the authors added.
