@article{Doris Steinemann_Larissa Arning_Inka Praulich_Manfred Stuhrmann_Henrik Hasle_Jan StarĂ½_Brigitte Schlegelberger_Charlotte M. Niemeyer_Christian Flotho_2010, place={Pavia, Italy}, title={Mitotic recombination and compound-heterozygous mutations are predominant NF1-inactivating mechanisms in children with juvenile myelomonocytic leukemia and neurofibromatosis type 1}, volume={95}, url={https://haematologica.org/article/view/5504}, DOI={10.3324/haematol.2009.010355}, abstractNote={Children with neurofibromatosis type 1 (NF-1), being constitutionally deficient for one allele of the <em>NF1</em> gene, are at greatly increased risk of juvenile myelomonocytic leukemia (JMML). <em>NF1</em> is a negative regulator of RAS pathway activity, which has a central role in JMML. To further clarify the role of biallelic <em>NF1</em> gene inactivation in the pathogenesis of JMML, we investigated the somatic <em>NF1</em> lesion in 10 samples from children with JMML/NF-1. We report that two-thirds of somatic events involved loss of heterozygosity (LOH) at the <em>NF1</em> locus, predominantly caused by segmental uniparental disomy of large parts of chromosome arm 17q. One-third of leukemias showed compound-heterozygous <em>NF1</em>-inactivating mutations. A minority of cases exhibited somatic interstitial deletions. The findings reinforce the emerging role of somatic mitotic recombination as a leukemogenic mechanism. In addition, they support the concept that biallelic <em>NF1</em&gt; inactivation in hematopoietic progenitor cells is required for transformation to JMML in children with NF-1.}, number={2}, journal={Haematologica}, author={Doris Steinemann and Larissa Arning and Inka Praulich and Manfred Stuhrmann and Henrik Hasle and Jan StarĂ½ and Brigitte Schlegelberger and Charlotte M. Niemeyer and Christian Flotho}, year={2010}, month={Feb.}, pages={320-323} }