Gene of the month:<i>KIT</i>

Roberts, Riyaadh; Govender, Dhirendra

doi:10.1136/jclinpath-2015-203207

Cited by 16 publications

(18 citation statements)

References 55 publications

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“…CD117 has been found to be present in a large assortment of tumours, including carcinomas, sarcomas, and haematopoietic malignancies. 8 However, when combined with morphology and other ancillary studies, it can be used in a panel to help differentiate a variety of entities. In fact, previous studies have shown that~30% of all myelomas are positive for CD117.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5] CD117, a type III tyrosine kinase receptor, is encoded by the KIT proto-oncogene, and shows aberrant expression in myelomatous plasma cells. 8,9 In fact, in one study of 13 cutaneous plasmacytomas, all 13 expressed CD117, including five that had plasmablastic morphology. 10 On the other hand, very few PBLs have been reported to express this protein.…”

Section: Introductionmentioning

confidence: 99%

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CD117 (KIT) is a useful marker in the diagnosis of plasmablastic plasma cell myeloma

2017

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CD117 (KIT) is a useful marker in the diagnosis of plasmablastic plasma cell myeloma

2017

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“…Mutated KIT homodimerizes in a ligand-independent way. Activated KIT initiates RAS/MAPK, PI3K/AKT/mTOR and JAK/STAT3 signaling [ 49 – 51 ] (Fig. 1 ).…”

Section: Introductionmentioning

confidence: 99%

“…Sporadically, melanoma, non-GIST stromal tumors and breast cancer have been signaled. KIT mutations could be implied in the arousal of the former [ 49 ]; the latter two are likely incidental. Sometimes, non-GIST signs are the first reason for patients to seek medical help [ 15 , 32 , 35 , 41 , 44 ].…”

Section: Introductionmentioning

confidence: 99%

Syndromic gastrointestinal stromal tumors

Ricci

2016

Hered Cancer Clin Pract

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of gastrointestinal tract. They feature heterogeneous triggering mechanisms, implying relevant clinical differences. The vast majority of GISTs are sporadic tumors. Rarely, however, GIST-prone syndromes occur, mostly depending on heritable GIST predisposing molecular defects involving the entire organism. These conditions need to be properly identified in order to plan appropriate diagnostic, prognostic and therapeutic procedures.Clinically, GIST-prone syndromes must be thought of whenever GISTs are multiple and/or associated with accompanying signs peculiar to the background tumorigenic trigger, either in single individuals or in kindreds. Moreover, syndromic GISTs, individually considered, tend to show distinctive features depending on the underlying condition. When applicable, genotyping is usually confirmatory.In GIST-prone conditions, the prognostic features of each GIST, defined according to the criteria routinely applied to sporadic GISTs, combine with the characters proper to the background syndromes, defining peculiar clinical settings which challenge physicians to undertake complex decisions. The latter concern preventive therapy and single tumor therapy, implying possible surgical and molecularly targeted options.In the absence of specific comprehensive guidelines, this review will highlight the traits characteristic of GIST-predisposing syndromes, with particular emphasis on diagnostic, prognostic and therapeutic implications, which can help the clinical management of these rare diseases.

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“…In mouse strains with KIT mutations several defects are observed such as anemia, infertility, susceptibility to infection, and pigment loss. Spontaneous mutations in KIT resulting in constitutive activation occur in human tumors including gastrointestinal stromal tumors (GIST), acute myelogenous leukemia (AML), melanoma, and systemic mastocytosis (4). Small molecule inhibitors that target KIT have had significant clinical success, most notably in the treatment of GIST where imatinib is now the standard of care for patients with high risk disease (5).…”

Section: Introductionmentioning

confidence: 99%

KTN0158, a Humanized Anti-KIT Monoclonal Antibody, Demonstrates Biologic Activity against both Normal and Malignant Canine Mast Cells

London

Gardner

Rippy

et al. 2017

Clinical Cancer Research

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Purpose KTN0158 is a novel anti-KIT antibody that potently inhibits wild-type and mutant KIT. This study evaluated the safety, biologic activity and pharmacokinetic/pharmacodynamics profile of KTN0158 in dogs with spontaneous mast cell tumors (MCT) as a prelude to human clinical applications. Experimental Design Cell proliferation, KIT phosphorylation and mast cell degranulation were evaluated in vitro. KTN0158 was administered to 4 research dogs to assess clinical effects and cutaneous mast cell numbers. Thirteen dogs with spontaneous MCT were enrolled into a prospective phase 1 dose-escalating open-label clinical study of KTN0158 evaluating 3 dose levels and 2 schedules and with weekly assessments for response and clinical toxicities. Results KTN0158 was a potent inhibitor of human and dog KIT activation and blocked mast cell degranulation in vitro. In dogs, KTN0158 was well tolerated and reduced cutaneous mast cell numbers in a dose-dependent manner. Clinical benefit of KTN0158 administration in dogs with MCT (n=5 partial response; n=7 stable disease) was observed regardless of KIT mutation status and decreased KIT phosphorylation was demonstrated in tumor samples. Histopathology after study completion demonstrated an absence of neoplastic cells in the primary tumors and/or metastatic lymph nodes from 4 dogs. Reversible hematologic and biochemical adverse events were observed at doses of 10 and 30 mg/kg. The maximum tolerated dose was established as 10 mg/kg. Conclusion KTN0158 inhibits KIT phosphorylation, demonstrates an acceptable safety profile in dogs, and provides objective responses in canine MCT patients with and without activating KIT mutations, supporting future clinical evaluation of KTN0158 in people.

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Gene of the month:KIT

Cited by 16 publications

References 55 publications

CD117 (KIT) is a useful marker in the diagnosis of plasmablastic plasma cell myeloma

CD117 (KIT) is a useful marker in the diagnosis of plasmablastic plasma cell myeloma

Syndromic gastrointestinal stromal tumors

KTN0158, a Humanized Anti-KIT Monoclonal Antibody, Demonstrates Biologic Activity against both Normal and Malignant Canine Mast Cells

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