SAMHD1 mutations in mantle cell lymphoma: identification as disease driver conferring in vitro resistance to nucleoside analogues

Bühler, M. M.; Lu, J.; Scheinost, S.; Nadeu, F.; Roos-Weil, D.; Hensel, M.; Thavayogarajah, T.; Moch, H.; Manz, M. G.; Haralambieva, E.; Marques Maggio, E.; Bea, S.; Gine, E.; Campo, E.; Bernard, O. A.; Huber, W.; Zenz, T.

doi:10.1101/2020.06.09.140376

bioRxiv · 10.1101/2020.06.09.140376

SAMHD1 mutations in mantle cell lymphoma: identification as disease driver conferring in vitro resistance to nucleoside analogues

Bühler, M. M.·Lu, J.·Scheinost, S.·Nadeu, F.·Roos-Weil, D.·Hensel, M.·Thavayogarajah, T.·Moch, H.·Manz, M. G.·Haralambieva, E.·Marques Maggio, E.·Bea, S.·Gine, E.·Campo, E.·Bernard, O. A.·Huber, W.·Zenz, T.

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Abstract

The genomic landscape of mantle cell lymphoma (MCL) includes frequent alterations of TP53, ATM, CCND1 and KMT2D. Thus far, the mutational landscape provides little information for treatment stratification. We characterized a cohort of MCL by targeted next generation sequencing and discovered SAMHD1 as a novel recurrently mutated gene (8.5% of investigated cases, 4/47 samples). Furthermore, we provide evidence of in vitro resistance of SAMHD1 mutated patient-derived MCL cells to cytarabine and fludarabine.

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Bühler, M. M., Lu, J., Scheinost, S., Nadeu, F., Roos-Weil, D., Hensel, M., Thavayogarajah, T., Moch, H., Manz, M. G., Haralambieva, E., Marques Maggio, E., Bea, S., Gine, E., Campo, E., Bernard, O. A., Huber, W., Zenz, T.. 2020-06-10. SAMHD1 mutations in mantle cell lymphoma: identification as disease driver conferring in vitro resistance to nucleoside analogues. https://doi.org/10.1101/2020.06.09.140376

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