HAEM5:Mast cell sarcoma: Difference between revisions

The presentation is variable. The disease is initially localized, followed by distant spread and a terminal phase resembling mast cell leukemia.<ref name=":1" /> Progression usually occurs quickly and prognosis is poor. Mast cell sarcoma often results in death within a few months.<ref name=":0" /> Treatment includes imatinib, a tyrosine kinase inhibitor that blocks [[PDGFRA|PDGF-R]] (platelet-derived growth factor receptor) and the tyrosine kinase proteins encoded by ''[[ABL1|abl]]'' (the Abelson proto-oncogene) and ''KIT'', or other tyrosine kinase inhibitors.<ref name=":2" /> Surgical debulking, radiation and chemotherapy are the usual first-line therapies.<ref>{{Cite journal|last=P|first=Valent|last2=C|first2=Akin|last3=Dd|first3=Metcalfe|date=2017|title=Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts|url=https://pubmed.ncbi.nlm.nih.gov/28031180/|language=en|doi=10.1182/blood-2016-09-731893|pmc=PMC5356454|pmid=28031180}}</ref><ref>{{Cite journal|last=Cr|first=Weiler|last2=J|first2=Butterfield|date=2014|title=Mast cell sarcoma: clinical management|url=https://pubmed.ncbi.nlm.nih.gov/24745684/|language=en|pmid=24745684}}</ref> Hematopoietic stem cell transplantation represents a potential curative treatment, but evidence of its efficacy is lacking.<ref name=":0" />

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==Sites of Involvement==

* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

The ''KIT'' Asp816Val mutation confers resistance to imatinib.<ref>{{Cite journal|last=C|first=Akin|last2=K|first2=Brockow|last3=C|first3=D'Ambrosio|last4=As|first4=Kirshenbaum|last5=Y|first5=Ma|last6=Bj|first6=Longley|last7=Dd|first7=Metcalfe|date=2003|title=Effects of tyrosine kinase inhibitor STI571 on human mast cells bearing wild-type or mutated c-kit|url=https://pubmed.ncbi.nlm.nih.gov/12901973/|language=en|pmid=12901973}}</ref> Other reported mutations in the ''KIT'' gene, including Asn822Lys and Leu779Phe, may also confer resistance to tyrosine kinase inhibitors, as suggested by patient outcomes and proximity to the tyrosine kinase domain.<ref name=":5" /><ref name=":4" />

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==Individual Region Genomic Gain / Loss / LOH==

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==Epigenomic Alterations==

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The ''KIT'' proto-oncogene encodes the KIT (CD117) tyrosine kinase protein receptor. KIT is found on hematopoietic progenitor cells, mast cells, germ cells, melanocytes, and interstitial cells of Cajal. Most hematopoietic stem cells loose KIT expression during maturation. However, mature mast cells continue to express KIT.  Stem Cell Factor protein is the ligand which binds to KIT protein, leading to dimerization and activation of signaling cascades involved in a wide variety of cellular roles, including regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function. In addition to mast cell disorders, mutations in this gene are found in gastrointestinal stromal tumors and acute myeloid leukemia.<ref>{{Cite journal|title=KIT - Mast/stem cell growth factor receptor Kit precursor - Homo sapiens (Human) - KIT gene & protein|url=https://www.uniprot.org/uniprot/P10721}}</ref><ref>{{Cite journal|last=L|first=Falchi|last2=S|first2=Verstovsek|date=2018|title=Kit Mutations: New Insights and Diagnostic Value|url=https://pubmed.ncbi.nlm.nih.gov/30007460/|language=en|pmid=30007460}}</ref>  

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==Genetic Diagnostic Testing Methods==