Genetic Test Predicts Bone Cancer Treatment Outcome

Molecular analysis of blood from patients with multiple myeloma can predict the risk of developing drug related neuropathy.

Genotyping of multiple myeloma patients can identify those that will show signs of peripheral neuropathy, which is a side effect of the common treatment regimens.

Scientists at the Institute of Cancer Research, (Sutton, UK), obtained peripheral-blood DNA samples were from 1,495 patients presenting with myeloma. Patient cases and controls were derived from two large clinical trials that compared thalidomide with conventional-based treatment in myeloma patients. DNA was extracted from frozen white blood cell pellets and genotyping was performed. A custom-built single nucleotide polymorphism (SNP) array was used to test the association of thalidomide-related peripheral neuropathy (TrPN) with 3,404 SNPs. The SNPs were selected in predicted functional regions within 964 genes spanning 67 molecular pathways thought to be involved in the pathogenesis, treatment response, and adverse effects associated with myeloma and its therapy.

In the patients who had been treated with thalidomide, they found five regions of DNA were more common in patients who had suffered neuropathy than those who had not developed the condition. The DNA was quantified using a NanoDrop Spectrophotometer, (NanoDrop Products, Wilmington, DE, USA). Interestingly, the regions are part of genes involved in repair, development, and inflammation of the peripheral nervous system. To determine whether the genes found were drug-specific, they ran the same scan on patients treated with vincristine and found that nine different genes were more common in patients who developed neuropathy. The finding indicates that each drug type causes neuropathy through a different biological pathway. Genotyping was performed using an Affymetrix Targeted genotyping True-tag array, (Affymetrix, Santa Clara, CA, USA).

Gareth J. Morgan, MD, a professor of hematology and lead author, said, "Doctors could use this simple and useful test to identify patients at high risk of neuropathy. At-risk patients could be closely monitored, and potentially given alternative treatments, lower doses, or additional therapy to reduce side effects. This knowledge may also help us develop treatments that could protect patients from neuropathy." This study also has implications for other cancer types as vincristine, for example, is commonly used to treat acute lymphoblastic leukemia and lymphoma. The study was published on March 1, 2011, in the Journal of Clinical Oncology.

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