{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:15:08Z","timestamp":1790241308670,"version":"4.1.0"},"reference-count":83,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>More than 90% of patients affected by mastocytosis are characterized by a somatic point mutation of KIT, which induces ligand-independent activation of the receptor and downstream signal triggering, ultimately leading to mast cell accumulation and survival. The most frequent mutation is KIT p.D816V, but other rarer mutations can also be found. These mutations often have a very low variant allele frequency (VAF), well below the sensitivity of common next-generation sequencing (NGS) methods used in routine diagnostic panels. Highly sensitive methods are developing for detecting mutations. This review summarizes the current indications on the recommended methods and on how to manage and interpret molecular data for the diagnosis and follow-up of patients with mastocytosis.<\/jats:p>","DOI":"10.3390\/ijms252010885","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T07:53:05Z","timestamp":1728546785000},"page":"10885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Detection of KIT Mutations in Systemic Mastocytosis: How, When, and Why"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6346-4791","authenticated-orcid":false,"given":"Daniela","family":"Cilloni","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, Mauriziano Hospital, 10128 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Maffeo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, Mauriziano Hospital, 10128 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Savi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, Mauriziano Hospital, 10128 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice Costanza","family":"Danzero","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, Mauriziano Hospital, 10128 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6491-8337","authenticated-orcid":false,"given":"Valentina","family":"Bonuomo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, Mauriziano Hospital, 10128 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Fava","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, Mauriziano Hospital, 10128 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"key":"ref_1","first-page":"1885","article-title":"Mast Cells, Mastocytosis, and Related Disorders","volume":"373","author":"Heybeli","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1093\/ajcp\/aqaa183","article-title":"Mastocytosis","volume":"155","author":"Tzankov","year":"2021","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10743","DOI":"10.7150\/thno.46719","article-title":"Mast Cells as a Unique Hematopoietic Lineage and Cell System: From Paul Ehrlich\u2019s Visions to Precision Medicine Concepts","volume":"10","author":"Valent","year":"2020","journal-title":"Theranostics"},{"key":"ref_4","first-page":"S18","article-title":"Activating Mutations of the C-Kit Proto-Oncogene in a Human Mast Cell Leukemia Cell Line","volume":"8","author":"Kanakura","year":"1994","journal-title":"Leukemia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1146\/annurev-pathol-052016-100312","article-title":"Pathogenesis and Pathology of Mastocytosis","volume":"12","author":"Metcalfe","year":"2017","journal-title":"Annu. Rev. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.leukres.2014.11.029","article-title":"The Impact of Sensitive KIT D816V Detection on Recognition of Indolent Systemic Mastocytosis","volume":"39","author":"Zanotti","year":"2015","journal-title":"Leuk. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e12319","DOI":"10.1002\/clt2.12319","article-title":"Cognitive, Neuropsychiatric and Neurological Alterations in Mastocytosis: A Systematic Review","volume":"13","year":"2023","journal-title":"Clin. Transl. Allergy"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e646","DOI":"10.1097\/HS9.0000000000000646","article-title":"Updated Diagnostic Criteria and Classification of Mast Cell Disorders: A Consensus Proposal","volume":"5","author":"Valent","year":"2021","journal-title":"Hemasphere"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th Edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic\/Dendritic Neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1182\/blood.2022015850","article-title":"International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: Integrating Morphologic, Clinical, and Genomic Data","volume":"140","author":"Arber","year":"2022","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1016\/j.jaci.2022.04.004","article-title":"Clinical Impact and Proposed Application of Molecular Markers, Genetic Variants, and Cytogenetic Analysis in Mast Cell Neoplasms: Status 2022","volume":"149","author":"Arock","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1016\/j.jaip.2023.08.008","article-title":"The Normal Range of Baseline Tryptase Should Be 1 to 15 Ng\/mL and Covers Healthy Individuals With H\u03b1T","volume":"11","author":"Valent","year":"2023","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1159\/000329856","article-title":"Validation of the REMA Score for Predicting Mast Cell Clonality and Systemic Mastocytosis in Patients with Systemic Mast Cell Activation Symptoms","volume":"157","author":"Matito","year":"2012","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.anai.2023.09.015","article-title":"Anaphylaxis: A 2023 Practice Parameter Update","volume":"132","author":"Golden","year":"2024","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.iac.2023.04.010","article-title":"Management of Mediator Symptoms, Allergy, and Anaphylaxis in Mastocytosis","volume":"43","author":"Gulen","year":"2023","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Giannetti, M.P., Nicoloro-SantaBarbara, J., Godwin, G., Middlesworth, J., Espeland, A., Douvas, J.L., and Castells, M.C. (2024). Challenges in Drug and Hymenoptera Venom Hypersensitivity Diagnosis and Management in Mastocytosis. Diagnostics, 14.","DOI":"10.3390\/diagnostics14020123"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1111\/cea.12318","article-title":"Risk Factors and Management of Severe Life-threatening Anaphylaxis in Patients with Clonal Mast Cell Disorders","volume":"44","author":"Valent","year":"2014","journal-title":"Clin. Exp. Allergy"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/j.bbrc.2005.09.150","article-title":"Structure and Regulation of Kit Protein-Tyrosine Kinase\u2014The Stem Cell Factor Receptor","volume":"338","author":"Roskoski","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/stem.5530110804","article-title":"Structure-Function Analyses of the Kit Receptor for the Steel Factor","volume":"11","author":"Blechman","year":"1996","journal-title":"Stem Cells"},{"key":"ref_20","first-page":"2207","article-title":"Organization and Nucleotide Sequence of the Human KIT (Mast\/Stem Cell Growth Factor Receptor) Proto-Oncogene","volume":"7","author":"Giebel","year":"1992","journal-title":"Oncogene"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.exphem.2013.05.005","article-title":"KIT GNNK Splice Variants: Expression in Systemic Mastocytosis and Influence on the Activating Potential of the D816V Mutation in Mast Cells","volume":"41","author":"Chan","year":"2013","journal-title":"Exp. Hematol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1634\/stemcells.2004-0117","article-title":"Normal and Oncogenic Forms of the Receptor Tyrosine Kinase Kit","volume":"23","author":"Lennartsson","year":"2005","journal-title":"Stem Cells"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1182\/blood.V82.4.1151.1151","article-title":"Expression of Isoforms of the Human Receptor Tyrosine Kinase C-Kit in Leukemic Cell Lines and Acute Myeloid Leukemia","volume":"82","author":"Crosier","year":"1993","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1152\/physrev.00046.2011","article-title":"Stem Cell Factor Receptor\/c-Kit: From Basic Science to Clinical Implications","volume":"92","author":"Lennartsson","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.ejphar.2005.12.067","article-title":"Stem Cell Factor and Its Receptor C-Kit as Targets for Inflammatory Diseases","volume":"533","author":"Reber","year":"2006","journal-title":"Eur. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1749-6632.2009.05122.x","article-title":"Signaling of C-kit in Dendritic Cells Influences Adaptive Immunity","volume":"1183","author":"Ray","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/nature07427","article-title":"Generation of a Prostate from a Single Adult Stem Cell","volume":"456","author":"Leong","year":"2008","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1159\/000106360","article-title":"Putative Human Liver Progenitor Cells in Explanted Liver","volume":"186","author":"Laurson","year":"2007","journal-title":"Cells Tissues Organs"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1161\/CIRCULATIONAHA.109.909093","article-title":"Cardiomyogenic Potential of C-Kit + \u2013Expressing Cells Derived From Neonatal and Adult Mouse Hearts","volume":"121","author":"Zaruba","year":"2010","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"435","DOI":"10.7150\/ijbs.6087","article-title":"The C-Kit Receptor-Mediated Signal Transduction and Tumor-Related Diseases","volume":"9","author":"Liang","year":"2013","journal-title":"Int. J. Biol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1042\/bj3410211","article-title":"Identification of Tyr-703 and Tyr-936 as the Primary Association Sites for Grb2 and Grb7 in the c-Kit\/Stem Cell Factor Receptor","volume":"341","author":"Lennartsson","year":"1999","journal-title":"Biochem. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1182\/blood.V98.5.1365","article-title":"Phosphatidylinositol 3 Kinase Contributes to the Transformation of Hematopoietic Cells by the D816V C-Kit Mutant","volume":"98","author":"Chian","year":"2001","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1182\/blood-2002-01-0177","article-title":"Necessity of Tyrosine 719 and Phosphatidylinositol 3\u2032-Kinase\u2013Mediated Signal Pathway in Constitutive Activation and Oncogenic Potential of c-Kit Receptor Tyrosine Kinase with the Asp814Val Mutation","volume":"101","author":"Hashimoto","year":"2003","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"27444","DOI":"10.1074\/jbc.M709703200","article-title":"Gab2 Is Involved in Differential Phosphoinositide 3-Kinase Signaling by Two Splice Forms of c-Kit","volume":"283","author":"Sun","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1042\/BJ20060464","article-title":"Direct Binding of Cbl to Tyr568 and Tyr936 of the Stem Cell Factor Receptor\/c-Kit Is Required for Ligand-Induced Ubiquitination, Internalization and Degradation","volume":"399","author":"Masson","year":"2006","journal-title":"Biochem. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1126\/science.279.5350.577","article-title":"Gain-of-Function Mutations of c-Kit in Human Gastrointestinal Stromal Tumors","volume":"279","author":"Hirota","year":"1998","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1081\/CNV-120027585","article-title":"Biology of Gastrointestinal Stromal Tumors: KIT Mutations and Beyond","volume":"22","author":"Duensing","year":"2004","journal-title":"Cancer Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4340","DOI":"10.1200\/JCO.2006.06.2984","article-title":"Somatic Activation of KIT in Distinct Subtypes of Melanoma","volume":"24","author":"Curtin","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1111\/j.1349-7006.2003.tb01470.x","article-title":"Alterations of the C-kit Gene in Testicular Germ Cell Tumors","volume":"94","author":"Sakuma","year":"2003","journal-title":"Cancer Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1073\/pnas.96.4.1609","article-title":"Activating and Dominant Inactivating C-KIT Catalytic Domain Mutations in Distinct Clinical Forms of Human Mastocytosis","volume":"96","author":"Longley","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","first-page":"920","article-title":"KIT Activating Mutations: Incidence in Adult and Pediatric Acute Myeloid Leukemia, and Identification of an Internal Tandem Duplication","volume":"89","author":"Beghini","year":"2004","journal-title":"Haematologica"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.iac.2023.04.008","article-title":"KIT Mutations and Other Genetic Defects in Mastocytosis","volume":"43","author":"Chantran","year":"2023","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1111\/all.15584","article-title":"KIT D816V Mutation in Blood for the Diagnostic Screening of Systemic Mastocytosis and Mast Cell Activation Syndromes","volume":"78","author":"Henriques","year":"2023","journal-title":"Allergy"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Nedoszytko, B., Arock, M., Lyons, J., Bachelot, G., Schwartz, L., Reiter, A., Jawhar, M., Schwaab, J., Lange, M., and Greiner, G. (2021). Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010411"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.iac.2014.01.009","article-title":"Molecular Defects in Mastocytosis","volume":"34","author":"Bibi","year":"2014","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/jid.2009.281","article-title":"Pediatric Mastocytosis Is a Clonal Disease Associated with D816V and Other Activating C-KIT Mutations","volume":"130","author":"Bodemer","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/labinvest.3700524","article-title":"Juxtamembrane-Type c-Kit Gene Mutation Found in Aggressive Systemic Mastocytosis Induces Imatinib-Resistant Constitutive KIT Activation","volume":"87","author":"Nakagomi","year":"2007","journal-title":"Lab. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1200\/JCO.2012.41.9549","article-title":"Mast Cell Sarcoma: A Rare and Aggressive Entity\u2014Report of Two Cases and Review of the Literature","volume":"31","author":"Aguilar","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00277-014-2207-9","article-title":"Chronic Mast Cell Leukemia (MCL) with KIT S476I: A Rare Entity Defined by Leukemic Expansion of Mature Mast Cells and Absence of Organ Damage","volume":"94","author":"Valent","year":"2015","journal-title":"Ann. Hematol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1111\/bjd.16795","article-title":"Paediatric Mastocytosis: Long-Term Follow-up of 53 Patients with Whole Sequencing of KIT. A Prospective Study","volume":"179","author":"Meni","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1016\/j.jaip.2022.03.001","article-title":"Standards of Genetic Testing in the Diagnosis and Prognostication of Systemic Mastocytosis in 2022: Recommendations of the EU-US Cooperative Group","volume":"10","author":"Hoermann","year":"2022","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Parente, R., Giudice, V., Cardamone, C., Serio, B., Selleri, C., and Triggiani, M. (2023). Secretory and Membrane-Associated Biomarkers of Mast Cell Activation and Proliferation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087071"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/S0145-2126(03)00093-6","article-title":"Multilineage Hematopoietic Involvement in Systemic Mastocytosis","volume":"27","author":"Akin","year":"2003","journal-title":"Leuk. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1182\/blood-2006-04-015545","article-title":"KIT Mutation in Mast Cells and Other Bone Marrow Hematopoietic Cell Lineages in Systemic Mast Cell Disorders: A Prospective Study of the Spanish Network on Mastocytosis (REMA) in a Series of 113 Patients","volume":"108","year":"2006","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.jaci.2009.05.003","article-title":"Prognosis in Adult Indolent Systemic Mastocytosis: A Long-Term Study of the Spanish Network on Mastocytosis in a Series of 145 Patients","volume":"124","author":"Escribano","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1002\/path.2677","article-title":"Variable Presence of KIT D816V in Clonal Haematological Non-mast Cell Lineage Diseases Associated with Systemic Mastocytosis (SM\u2013AHNMD)","volume":"220","author":"Sotlar","year":"2010","journal-title":"J. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1038\/leu.2015.4","article-title":"Molecular Profiling of Myeloid Progenitor Cells in Multi-Mutated Advanced Systemic Mastocytosis Identifies KIT D816V as a Distinct and Late Event","volume":"29","author":"Jawhar","year":"2015","journal-title":"Leukemia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1158\/0008-5472.CAN-16-2234","article-title":"Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future","volume":"77","author":"Valent","year":"2017","journal-title":"Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"18250","DOI":"10.18632\/oncotarget.4213","article-title":"Mastocytosis: A mutated KIT receptor induced myeloproliferative disorder","volume":"21","author":"Chatterjee","year":"2015","journal-title":"Oncotarget"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ke, H., Kazi, J.U., Zhao, H., and Sun, J. (2016). Germline mutations of KIT in gastrointestinal stromal tumor (GIST) and mastocytosis. Cell Biosci., 6.","DOI":"10.1186\/s13578-016-0120-8"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1016\/j.jaip.2020.12.049","article-title":"Detection of the germline KIT S476I mutation in a kindred with familial mastocytosis associated with gastrointestinal stromal tumors","volume":"9","author":"Peters","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1146\/annurev-pathmechdis-031521-042618","article-title":"New Insights into the Pathogenesis of Mastocytosis: Emerging Concepts in Diagnosi and Therapy","volume":"18","author":"Valent","year":"2023","journal-title":"Annu. Rev. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/ejh.12043","article-title":"Advanced systemic mastocytosis: The impact of KIT mutations in diagnosis, treatment, and progression","volume":"90","author":"Verstovsek","year":"2013","journal-title":"Eur. J. Haematol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"726.e1","DOI":"10.1016\/j.jaci.2009.10.020","article-title":"Mast cells from different molecular and prognostic subtypes of systemic mastocytosis display distinct immunophenotypes","volume":"125","author":"Teodosio","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/ajh.23672","article-title":"Sensitive KIT D816V Mutation Analysis of Blood as a Diagnostic Test in Mastocytosis","volume":"89","author":"Kristensen","year":"2014","journal-title":"Am. J. Hematol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00277-013-1964-1","article-title":"The KIT D816V Expressed Allele Burden for Diagnosis and Disease Monitoring of Systemic Mastocytosis","volume":"93","author":"Erben","year":"2014","journal-title":"Ann. Hematol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1373\/clinchem.2017.277897","article-title":"Digital PCR: A Sensitive and Precise Method for KIT D816V Quantification in Mastocytosis","volume":"64","author":"Greiner","year":"2018","journal-title":"Clin. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"8604","DOI":"10.1021\/ac202028g","article-title":"High-Throughput Droplet Digital PCR System for Absolute Quantitation of DNA Copy Number","volume":"83","author":"Hindson","year":"2011","journal-title":"Anal. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1373\/clinchem.2014.221366","article-title":"Considerations for Digital PCR as an Accurate Molecular Diagnostic Tool","volume":"61","author":"Huggett","year":"2015","journal-title":"Clin. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/ejh.12601","article-title":"Targeted Ultradeep Next-Generation Sequencing as a Method for KIT D816V Mutation Analysis in Mastocytosis","volume":"96","author":"Kristensen","year":"2016","journal-title":"Eur. J. Haematol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Naumann, N., L\u00fcbke, J., Baumann, S., Schwaab, J., Hoffmann, O., Kreil, S., Dangelo, V., Reiter, L., Bugert, P., and Kristensen, T. (2021). Adverse Prognostic Impact of the KIT D816V Transcriptional Activity in Advanced Systemic Mastocytosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052562"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/bjh.14123","article-title":"Comparison of gDNA-based versus mRNA-based KIT D816V Mutation Analysis Reveals Large Differences between Blood and Bone Marrow in Systemic Mastocytosis","volume":"178","author":"Kristensen","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"366","DOI":"10.3324\/haematol.2019.217950","article-title":"Molecular Quantification of Tissue Disease Burden Is a New Biomarker and Independent Predictor of Survival in Mastocytosis","volume":"105","author":"Greiner","year":"2020","journal-title":"Haematologica"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1111\/all.12409","article-title":"The KIT D 816 V Allele Burden Predicts Survival in Patients with Mastocytosis and Correlates with the WHO Type of the Disease","volume":"69","author":"Hoermann","year":"2014","journal-title":"Allergy"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1182\/blood-2017-01-764423","article-title":"Response and Progression on Midostaurin in Advanced Systemic Mastocytosis: KIT D816V and Other Molecular Markers","volume":"130","author":"Jawhar","year":"2017","journal-title":"Blood"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5750","DOI":"10.1182\/bloodadvances.2022007539","article-title":"Efficacy and Safety of Avapritinib in Previously Treated Patients with Advanced Systemic Mastocytosis","volume":"6","author":"Reiter","year":"2022","journal-title":"Blood Adv."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/leu.2009.37","article-title":"Frequent TET2 Mutations in Systemic Mastocytosis: Clinical, KITD816V and FIP1L1-PDGFRA Correlates","volume":"23","author":"Tefferi","year":"2009","journal-title":"Leukemia"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Traina, F., Visconte, V., Jankowska, A.M., Makishima, H., O\u2019Keefe, C.L., Elson, P., Han, Y., Hsieh, F.H., Sekeres, M.A., and Mali, R.S. (2012). Single Nucleotide Polymorphism Array Lesions, TET2, DNMT3A, ASXL1 and CBL Mutations Are Present in Systemic Mastocytosis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043090"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.1182\/blood-2011-12-397588","article-title":"In Aggressive Forms of Mastocytosis, TET2 Loss Cooperates with c-KITD816V to Transform Mast Cells","volume":"120","author":"Soucie","year":"2012","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1182\/blood-2013-04-496448","article-title":"Comprehensive Mutational Profiling in Advanced Systemic Mastocytosis","volume":"122","author":"Schwaab","year":"2013","journal-title":"Blood"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/leu.2015.284","article-title":"Additional Mutations in SRSF2, ASXL1 and\/or RUNX1 Identify a High-Risk Group of Patients with KIT D816V+ Advanced Systemic Mastocytosis","volume":"30","author":"Jawhar","year":"2016","journal-title":"Leukemia"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/gcc.22526","article-title":"Incidence and Prognostic Impact of Cytogenetic Aberrations in Patients with Systemic Mastocytosis","volume":"57","author":"Naumann","year":"2018","journal-title":"Genes. Chromosomes Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"292","DOI":"10.7150\/thno.51872","article-title":"Cytogenetic and Molecular Aberrations and Worse Outcome for Male Patients in Systemic Mastocytosis","volume":"11","author":"Jawhar","year":"2021","journal-title":"Theranostics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/20\/10885\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:10:24Z","timestamp":1760112624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/20\/10885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,10]]},"references-count":83,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ijms252010885"],"URL":"https:\/\/doi.org\/10.3390\/ijms252010885","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,10]]}}}