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New genetic clues to why most bone marrow transplant patients develop graft-versus-host disease
Date:9/4/2012

tionally used to match recipients and donors, a process called tissue typing.

Researchers found that if a patient and donor have different SNPs, the patient was at increased risk of GVHD or a lower chance of disease-free survival. The scientists surmised that genes located near these SNPs must be involved in that process.

"The question I wanted to ask with this study is whether there could be genes we don't know about that are located close to the major histocompatibility complex that could be influencing GVHD risk," said Petersdorf, a member of the Hutchinson Center's Clinical Research Division. "Now that we know what to test for we can begin screening for the presence of the SNPs in patients and donors and select the optimal donor whose SNP profile will benefit the patient the most."

SNP genotyping is only beneficial for patients when they have multiple matched unrelated donors in order to determine which donor is the optimal match. Fortunately, this is fairly common, according to the study. Of 230 patients who had two or more HLA-matched donors, significant percentages also had at least one donor who was SNP-matched.

A SNP is a base change that involves two or more of the four bases (A, C, T and G) that comprise DNA, and is the simplest form of DNA variation on the human genome. SNPs serve as signposts or markers for nearby genes that are the actual drivers for the effect that they have on disease.

The next step for researchers is to sequence the MHC region of genes close to the SNP locations in order to identify which genes are directly responsible for the correlations of survival and GVHD.

"Once we discover those genes we will characterize them and then we may be able to further refine donor matching," Petersdorf said.

For this study, researchers conducted a retrospective discovery-validation study that examined DNA from more than 4,000 former transplant patients nationwide. They studied 1,120 SNPs in t
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Contact: Dean Forbes
dforbes@fhcrc.org
206-667-2896
Fred Hutchinson Cancer Research Center
Source:Eurekalert

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