Who am I? Optimal Tissue for Germline Genetic Testing Post-Stem Cell Transplantation

Mertens, M.; Sadlo, M.; Kuehl, J. S.; Metzeler, K.; Zschenderlein, L.; Edelmann, J.; Lehmann, C.; Tull, S.; Karakaya, M.; Velmans, C.; Tumewu, T.; Boehme, M.; Kloetzer, C.; Weigert, A.; Hentschel, J.

doi:10.1101/2025.01.20.630521

bioRxiv · 10.1101/2025.01.20.630521

Who am I? Optimal Tissue for Germline Genetic Testing Post-Stem Cell Transplantation

Mertens, M.·Sadlo, M.·Kuehl, J. S.·Metzeler, K.·Zschenderlein, L.·Edelmann, J.·Lehmann, C.·Tull, S.·Karakaya, M.·Velmans, C.·Tumewu, T.·Boehme, M.·Kloetzer, C.·Weigert, A.·Hentschel, J.

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Abstract

With advancements in genetic diagnostics and genotype-based therapeutics, the demand for germline genetic testing in post-hematopoietic stem cell transplantation patients is increasing. Due to genetic chimerism, blood samples can no longer be used for germline testing after transplantation. This study aims to identify the most suitable tissue for germline analysis following stem cell transplantation by investigating alternative tissue sources. Buccal swab, eyebrow hair, and nail samples were analyzed for donor-derived DNA using next-generation sequencing and short tandem repeat analysis, with linear regression used for evaluation. Factors such as HLA match, transplantation type, sex, and time after transplantation were also evaluated for their effect on donor-derived DNA share. Buccal swab and nail samples exhibited 25% and 22% higher proportions of donor-derived DNA compared to eyebrow hair follicles, respectively. The median donor DNA share in eyebrow hair follicles was 1% for NGS and 3% for STR. Factors such as matched related donors, higher HLA match, different donor-recipient sex, and longer time post-transplantation correlated with lower donor DNA shares. Eyebrow hair follicles are a promising tissue for accurate germline genetic testing in post-SCT patients. Patient characteristics like donor relatedness, HLA match, sex match, and time after transplantation should be considered.

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Mertens, M., Sadlo, M., Kuehl, J. S., Metzeler, K., Zschenderlein, L., Edelmann, J., Lehmann, C., Tull, S., Karakaya, M., Velmans, C., Tumewu, T., Boehme, M., Kloetzer, C., Weigert, A., Hentschel, J.. 2025-01-24. Who am I? Optimal Tissue for Germline Genetic Testing Post-Stem Cell Transplantation. https://doi.org/10.1101/2025.01.20.630521

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