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523-Gene Panel Reveals Treatment Targets for Leukemia

523-Gene Panel Reveals Treatment Targets for Leukemia

523-Gene Panel Reveals Treatment Targets for Leukemia

523-Gene Panel Reveals Treatment Targets for Leukemia

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A gene panel that looks for about 10 times the number of cancer-causing genes as panels currently used to diagnose and fine tune treatment for a variety of cancers is effective at identifying problematic genes in the most common leukemia, investigators report.

The 523-gene panel, developed by San Diego-based biotech company Illumina, which includes all genes known to potentially cause cancer, can be readily adopted for use in clinical laboratories to diagnose acute myeloid leukemia, or AML, the investigators report in the journal PLOS ONE.

Identifying more genetic mutations in an individual's cancer also enables more targeted treatment for that patient, they say. That includes finding mutations not previously associated with their cancer type, which opens the door to using drugs targeting those mutations that have traditionally been used against other cancers.

"Having a bigger panel gives us more targets," says Dr. Ravindra Kolhe, vice chair for translational research in the Department of Pathology at the Medical College of Georgia at Augusta University.

"Part of what we found here is this 523-panel works for leukemia and that it's a practical and clinically relevant tool for clinical laboratories for routine molecular profiling of blood cancer," says Kolhe, the study's corresponding author.

AML is a distinct disease in every patient because, as investigators are increasingly learning, the gene mutations involved may not be the same in any two patients, says Dr. Vamsi Kota, MCG hematologist/oncologist who directs the Bone Marrow and Stem Cell Transplant Program at the Georgia Cancer Center and AU Health.

"The term 'leukemia' is broad and we should not be treating everyone the same," says Kota, a study coauthor. "That is one of the reasons you see the same treatment working for some and not working for others."

The MCG investigators retrospectively analyzed 61 bone marrow samples, which included samples from 40 patients with confirmed leukemia and detailed clinical information on 27 of those patients.

The larger panel identified 880 variants in 292 genes, and only 14.8% of the variants were in genes included in the smaller 54-gene panel currently in use by many labs, they write. The remaining 749 variants are not typically assessed in a leukemia diagnosis or detected by the 54-gene panel, they note.

When they looked at the information available on those 749 variants in follow up, they found at least 14 of the variants in 10 genes likely could contribute to AML and 96.2% of the patients had at least one of the 14 novel variants. They also found 22 variants in five other genes associated with other tumor types in the vast majority of the patients with AML.

Novel variants identified in the patients might be significant in providing a more complete diagnosis and prognosis for patients and in better identifying treatment that more directly targets their cancer-associated mutations, they say.

There is often overlap in the mutations that contributes to different types of cancer and the broader assessment of mutations present should help identify those.

"The more we know, the more it expands our knowledge of leukemia and expands our ways to treat it," Kota says. "If you find something abnormal in the genes, which is there in other cancers, then we can use those drugs in these patients," Kolhe adds.

"The hope is by finding more of these mutations, we no longer call the cancer by a name but we call it-- and treat it -- by the mutations," says Kota.

Reference: Sahajpal NS, Mondal AK, Ananth S, et al. Clinical performance and utility of a comprehensive next-generation sequencing DNA panel for the simultaneous analysis of variants, TMB and MSI for myeloid neoplasms. PLOS ONE. 2020;15(10):e0240976. doi:10.1371/journal.pone.0240976

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