TUESDAY, April 19 (HealthDay News) -- Whole-genome sequencing appears to be effective in identifying cryptic mutations in cancer susceptibility genes, according to two studies published in the April 20 issue of the Journal of the American Medical Association.
To identify rare or novel germline variants in cancer susceptibility genes, Daniel C. Link, M.D., of Washington University in St. Louis, and colleagues applied whole-genome sequencing on normal skin and leukemic cells in a patient without any significant family history of cancer but with suspected increased cancer susceptibility because of multiple primary tumors. The patient had early-onset breast and ovarian cancer and therapy-related acute myeloid leukemia. Whole genome sequencing identified novel, cryptic variants in cancer susceptibility genes and provided unbiased information on the spectrum of mutations in a cancer genome.
John S. Welch, M.D., Ph.D., of Washington University, and colleagues aimed to determine whether whole-genome sequencing identified cryptic, actionable mutations in a clinically relevant time frame. In a difficult diagnostic case of acute promyelocytic leukemia with no pathogenic X-RARA fusion, the investigators used paired-end-read whole-genome sequencing for real-time oncologic diagnosis and described the genomic details of an oncogenic fusion gene created by an insertional event. In validating a novel insertional fusion that created a classic PML-RARA bcr3 variant, the investigators altered the medical care of the patient, who received all-trans retinoic acid consolidation instead of an allogeneic stem cell transplant. Therefore, they showed whole-genome sequencing can identify cytogenetically invisible oncogenes in a clinically relevant time period.
"These cases of personalized genomic medicine are just some of the first examples of what will likely be commonplace in the near future. New innovations in DNA sequencing are expected to increase the speed of data collection and decrease the costs by another order of magnitude in the next two years," write the authors of an accompanying editorial.
One author of the second study disclosed financial ties to Celgene and Novartis, while another author disclosed ties to Genzyme. One author of the accompanying editorial disclosed financial relationships with Amgen and TheraBionic.
Abstract - Link
Full Text (subscription or payment may be required)
Abstract - Welch
Full Text (subscription or payment may be required)
Editorial (subscription or payment may be required)
