{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNeurofibromin—the protein encoded by the NF1 gene—is a key tumor suppressor that serves primarily as a RAS GTPase–activating protein. By accelerating the hydrolysis of active RAS–GTP to its inactive RAS–GDP form, neurofibromin downregulates mitogenic signaling cascades such as the RAF/MEK/ERK pathway. This fundamental function is central to proper cell growth, differentiation, and maintenance of neural crest–derived lineages, and disturbances in this regulatory mechanism underlie the molecular basis of neurofibromatosis type 1."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn many cancers, loss-of-function NF1 mutations remove this negative control on RAS signaling and thereby drive uncontrolled proliferation. In glioblastoma, melanoma, lung cancers and other malignancies, NF1 deficiency has been associated with distinct oncogenic subtypes and with resistance to targeted agents such as RAF and MEK inhibitors. The deregulated RAS/MAPK cascade that ensues after neurofibromin loss is now recognized as both a driver of tumorigenesis and a mechanism by which tumors acquire therapeutic resistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "13"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in neoplasia, NF1 is crucial for normal neural and developmental processes. In the central nervous system, NF1 loss affects astrocyte growth regulation and impairs working memory by altering inhibitory circuit dynamics. Similarly, NF1 haploinsufficiency in non‐neuronal cells contributes to aberrant bone remodeling, as seen in increased osteoclast activity and osseous dysplasias. These studies demonstrate that neurofibromin function is vital not only to tumor suppression but also to proper neurodevelopment and skeletal homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "20"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA complex spectrum of NF1 gene alterations—including intragenic missense mutations, small in‐frame deletions, and large microdeletions—has been associated with highly variable clinical phenotypes. Certain alleles predispose to a milder presentation with fewer cutaneous or plexiform neurofibromas sometimes accompanied by Noonan‐like features, whereas others correlate with increased tumor burden and malignant progression. These genotype–phenotype correlations highlight the importance of both the type and location of NF1 mutations, as well as the influence of secondary events, in determining disease severity and therapeutic response."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "30"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent mechanistic insights have suggested promising avenues for precision therapy in NF1‐deficient tumors. In preclinical models, targeting downstream effectors—whether by inhibiting MEK/ERK, SHP2 phosphatase, or components of the PI3K/mTOR axis—can restore the balance of RAS signaling and overcome drug resistance. Moreover, NF1 inactivation has been linked to activation of stress response pathways (for example, via HSF1) and has been identified as a mutational target in mismatch repair–deficient contexts. Emerging data on the tumor microenvironment further implicate NF1 loss in promoting paracrine signals that enhance collagen deposition and tumor invasion. Collectively, these findings underscore the therapeutic potential of combinatorial strategies aimed at the diverse molecular consequences of NF1 deficiency."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "31", "end_ref": "33"}]}, {"type": "t", "text": ""}]}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S A Rasmussen, J M Friedman "}, {"type": "b", "children": [{"type": "t", "text": "NF1 gene and neurofibromatosis 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Epidemiol (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/oxfordjournals.aje.a010118"}], "href": "https://doi.org/10.1093/oxfordjournals.aje.a010118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10625171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10625171"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "A B Trovó-Marqui, E H Tajara "}, {"type": "b", "children": [{"type": "t", "text": "Neurofibromin: a general outlook."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-0004.2006.00639.x"}], "href": "https://doi.org/10.1111/j.1399-0004.2006.00639.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16813595"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16813595"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Irma B Stowe, Ellen L Mercado, Timothy R Stowe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.190876.112"}], "href": "https://doi.org/10.1101/gad.190876.112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22751498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22751498"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Charlotte Philpott, Hannah Tovell, Ian M Frayling, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The NF1 somatic mutational landscape in sporadic human cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genomics (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40246-017-0109-3"}], "href": "https://doi.org/10.1186/s40246-017-0109-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28637487"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28637487"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Roel G W Verhaak, Katherine A Hoadley, Elizabeth Purdom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2009.12.020"}], "href": "https://doi.org/10.1016/j.ccr.2009.12.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20129251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20129251"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Robert J Nichols, Franziska Haderk, Carlos Stahlhut, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RAS nucleotide cycling underlies the SHP2 phosphatase dependence of mutant BRAF-, NF1- and RAS-driven cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41556-018-0169-1"}], "href": "https://doi.org/10.1038/s41556-018-0169-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30104724"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30104724"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Michael Krauthammer, Yong Kong, Antonella Bacchiocchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.3361"}], "href": "https://doi.org/10.1038/ng.3361"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26214590"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26214590"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Steven R Whittaker, Jean-Philippe Theurillat, Eliezer Van Allen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-scale RNA interference screen implicates NF1 loss in resistance to RAF inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Discov (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/2159-8290.CD-12-0470"}], "href": "https://doi.org/10.1158/2159-8290.CD-12-0470"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23288408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23288408"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Moriah H Nissan, Christine A Pratilas, Alexis M Jones, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK dependence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-13-2625"}], "href": "https://doi.org/10.1158/0008-5472.CAN-13-2625"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24576830"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24576830"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Maija Kiuru, Klaus J Busam "}, {"type": "b", "children": [{"type": "t", "text": "The NF1 gene in tumor syndromes and melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lab Invest (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/labinvest.2016.142"}], "href": "https://doi.org/10.1038/labinvest.2016.142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28067895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28067895"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Helena Cirenajwis, Martin Lauss, Henrik Ekedahl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NF1-mutated melanoma tumors harbor distinct clinical and biological characteristics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.12050"}], "href": "https://doi.org/10.1002/1878-0261.12050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28267273"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28267273"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Wendy L See, I-Li Tan, Joydeep Mukherjee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sensitivity of glioblastomas to clinically available MEK inhibitors is defined by neurofibromin 1 deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-12-0334"}], "href": "https://doi.org/10.1158/0008-5472.CAN-12-0334"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22573716"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22573716"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Thomas Wiesner, Maija Kiuru, Sasinya N Scott, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NF1 Mutations Are Common in Desmoplastic Melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Surg Pathol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/PAS.0000000000000451"}], "href": "https://doi.org/10.1097/PAS.0000000000000451"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26076063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26076063"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Michaela Livia Bajenaru, Yuan Zhu, Nicolé M Hedrick, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Astrocyte-specific inactivation of the neurofibromatosis 1 gene (NF1) is insufficient for astrocytoma formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.22.14.5100-5113.2002"}], "href": "https://doi.org/10.1128/MCB.22.14.5100-5113.2002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12077339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12077339"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "M Upadhyaya, S M Huson, M Davies, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in exon 17 of the NF1 gene (c.2970-2972 delAAT): evidence of a clinically significant NF1 genotype-phenotype correlation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/510781"}], "href": "https://doi.org/10.1086/510781"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17160901"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17160901"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Carrie Shilyansky, Katherine H Karlsgodt, Damian M Cummings, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neurofibromin regulates corticostriatal inhibitory networks during working memory performance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1004829107"}], "href": "https://doi.org/10.1073/pnas.1004829107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20624961"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20624961"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Kitiwan Rojnueangnit, Jing Xie, Alicia Gomes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High Incidence of Noonan Syndrome Features Including Short Stature and Pulmonic Stenosis in Patients carrying NF1 Missense Mutations Affecting p.Arg1809: Genotype-Phenotype Correlation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22832"}], "href": "https://doi.org/10.1002/humu.22832"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26178382"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26178382"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Kelly A Diggs-Andrews, Jacquelyn A Brown, Scott M Gianino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sex Is a major determinant of neuronal dysfunction in neurofibromatosis type 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.24093"}], "href": "https://doi.org/10.1002/ana.24093"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24375753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24375753"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "David A Stevenson, Holly Zhou, Shadi Ashrafi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Double inactivation of NF1 in tibial pseudarthrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/504441"}], "href": "https://doi.org/10.1086/504441"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16773574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16773574"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Audrey Sabbagh, Eric Pasmant, Ingrid Laurendeau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Unravelling the genetic basis of variable clinical expression in neurofibromatosis 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp212"}], "href": "https://doi.org/10.1093/hmg/ddp212"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19417008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19417008"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Lan Kluwe, Reiner Siebert, Stefan Gesk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Screening 500 unselected neurofibromatosis 1 patients for deletions of the NF1 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.10299"}], "href": "https://doi.org/10.1002/humu.10299"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14722914"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14722914"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "V-F Mautner, L Kluwe, R E Friedrich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2009.075937"}], "href": "https://doi.org/10.1136/jmg.2009.075937"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20543202"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20543202"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Alessandro De Luca, Irene Bottillo, Anna Sarkozy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/498454"}], "href": "https://doi.org/10.1086/498454"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16380919"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16380919"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Grant W Simmons, Winnie W Pong, Ryan J Emnett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neurofibromatosis-1 heterozygosity increases microglia in a spatially and temporally restricted pattern relevant to mouse optic glioma formation and growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neuropathol Exp Neurol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/NEN.0b013e3182032d37"}], "href": "https://doi.org/10.1097/NEN.0b013e3182032d37"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21157378"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21157378"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Nelly Burnichon, Alexandre Buffet, Béatrice Parfait, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Somatic NF1 inactivation is a frequent event in sporadic pheochromocytoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/dds374"}], "href": "https://doi.org/10.1093/hmg/dds374"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22962301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22962301"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Brian V Balgobind, Pieter Van Vlierberghe, Ans M W van den Ouweland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-06-095075"}], "href": "https://doi.org/10.1182/blood-2007-06-095075"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18172006"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18172006"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Jenny Welander, Catharina Larsson, Martin Bäckdahl, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Elevated risk for MPNST in NF1 microdeletion patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/374821"}], "href": "https://doi.org/10.1086/374821"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12660952"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12660952"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Ophélia Maertens, Bryan Johnson, Pablo Hollstein, et al. 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