Sinonasal, genital and acrolentiginous melanomas show distinct characteristics of KIT expression and mutations

Schoenewolf, Nicola L.; Bull, Christian; Belloni, Benedetta; Holzmann, David; Tonolla, Sabina; Lang, Roland; Mihic‐Probst, Daniela; Andrés, Christian; Dummer, Reinhard

doi:10.1016/j.ejca.2012.02.049

Cited by 69 publications

(49 citation statements)

References 40 publications

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“…Lack of cKIT mutations in SNMs from this study is consistent with the findings recently reported by Schoenewolf et al [11], further indicating that melanoma at this anatomic site may present a much lower frequency of cKIT mutations than mucosal melanomas of other sites. As a confirmation of such a heterogeneous mutation distribution, occurrence of cKIT mutations (18%) was found in our subset of acral melanomas from the same geographic area.…”

Section: Discussionsupporting

confidence: 82%

“…The cKIT gene has been widely recognized as genetically altered in 10-35% of mucosal melanomas [7,8,11,19,20]. This wide range of mutation rates mostly depends on the anatomic origin of this type of tumor, with the highest (35%) and the lowest (10%) mutation frequency reported in vulvovaginal melanomas and SNMs, respectively [11].…”

Section: Discussionmentioning

confidence: 99%

“…This wide range of mutation rates mostly depends on the anatomic origin of this type of tumor, with the highest (35%) and the lowest (10%) mutation frequency reported in vulvovaginal melanomas and SNMs, respectively [11]. Generally, cKIT mutations seem to be more common in mucosal and acral melanomas compared with cutaneous melanomas and are sometimes accompanied by amplification of the cKIT gene [15].…”

Section: Discussionmentioning

confidence: 99%

“…In particular, an increased prevalence of activating cKIT mutations, mostly accompanied by gene overexpression and/or amplification and, to a less extent, of BRAF and NRAS mutations has been described in a specific subset of mucosal melanomas [9,10,11]. …”

Section: Introductionmentioning

confidence: 99%

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Unexpected Distribution of cKIT and BRAF Mutations among Southern Italian Patients with Sinonasal Melanoma

et al. 2013

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Background: Racial and geographic factors seem to affect the incidence of cutaneous and mucosal melanoma. Objective: To investigate the occurrence of BRAF and cKIT impairments in patients with sinonasal melanoma in Southern Italy. Methods: Eleven sinonasal melanomas were screened for BRAF mutations and cKIT alterations by immunohistochemistry (CD117), fluorescence in situ hybridization and sequencing analyses. Results: A high prevalence (4/11; 36%) of BRAF mutations and lack of cKIT mutations were observed. Amplification of cKIT was found in 18% of cases; cKIT expression was detectable in 18% non-overlapping cases. No correlation between CD117 and cKIT alterations was observed. One (6%) cKIT and two (12%) BRAF mutations were detected in an additional series of 17 acral/mucosal melanomas from the same geographic areas. Conclusion: Mutations of cKIT are infrequent in sinonasal melanoma in Southern Italy.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Unexpected Distribution of cKIT and BRAF Mutations among Southern Italian Patients with Sinonasal Melanoma

et al. 2013

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“…Approximately 15% of mucosal (with an especially high mutation rate in vulvovaginal melanomas 43 ) and 23% of acral melanomas have a mutation or amplification in KIT, 44 which could allow therapy with specific inhibitors. A phase 2 trial of imatinib 800 mg/d in Chinese patients reported a partial response rate of 23% and stabilization in 30% of patients.…”

Section: Kit Inhibitorsmentioning

confidence: 99%

Treatment Algorithms in Stage IV Melanoma

Espinosa

Grob

Dummer

et al. 2015

American Journal of Therapeutics

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The molecular classification of melanoma and the advent of new drugs are changing the paradigm of therapy for advanced melanoma. A review of the recent key studies was performed, followed by a discussion in an expert forum. The aim of this review was to generate a therapeutic algorithm for stage IV melanoma. Tumor genotyping for BRAF and/or KIT should be performed before selection of therapy. For most BRAF-mutated melanoma patients and particularly those with a high tumor load, vemurafenib or other BRAF inhibitors such as dabrafenib are the treatment of choice. KIT inhibitors can be effective in KIT-mutant tumors, especially in those patients with mutations at exons 11 and 13. Ipilimumab is a good option for patients with nontargetable or nondetected mutations and those who progress under therapy with vemurafenib or a KIT inhibitor. There is still a role for conventional chemotherapy either as first-line treatment in BRAF wild-type patients or as salvage therapy in second or third line, or after other treatment modalities. Participation in clinical trials is strongly encouraged, either in first or in subsequent lines. New therapeutic options for advanced melanoma are guided by tumor genotyping. The current therapeutic algorithm includes kinase inhibitors, anti-CTLA4 therapy, immunotherapy, and chemotherapy, depending on the tumor genotype and response to previous treatments. Participation in clinical trials should always be encouraged because the treatment goal is long-term survival and potential cure in a subset of patients. The molecular classification of melanoma and the advent of new drugs are changing the paradigm of therapy for advanced melanoma. A review of the recent key studies was performed, followed by a discussion in an expert forum. The aim of this review was to generate a therapeutic algorithm for stage IV melanoma. Tumor genotyping for BRAF and/or KIT should be performed before selection of therapy. For most BRAF-mutated melanoma patients and particularly those with a high tumor load, vemurafenib or other BRAF inhibitors such as dabrafenib are the treatment of choice. KIT inhibitors can be effective in KIT-mutant tumors, especially in those patients with mutations at exons 11 and 13. Ipilimumab is a good option for patients with nontargetable or nondetected mutations and those who progress under therapy with vemurafenib or a KIT inhibitor. There is still a role for conventional chemotherapy either as first-line treatment in BRAF wild-type patients or as salvage therapy in second or third line, or after other treatment modalities. Participation in clinical trials is strongly encouraged, either in first or in subsequent lines. New therapeutic options for advanced melanoma are guided by tumor genotyping. The current therapeutic algorithm includes kinase inhibitors, anti-CTLA4 therapy, immunotherapy, and chemotherapy, depending on the tumor genotype and response to previous treatments. Participation in clinical trials should always be encouraged because the treatment goal is long-term surviv...

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Systemic Treatment of Melanoma

Dummer,

Goldinger

2024

Rook's Textbook of Dermatology

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Systemic therapy for melanoma patients has dramatically improved over the past decade. New treatment strategies have significantly ameliorated survival and prognosis of affected patients. The indication for immune directed and targeted therapies has expanded and can be considered for both very early melanoma stages as well as advanced disease. Ongoing challenges deal with reducing development of primary and secondary resistance to antitumoural drugs and identifying useful biomarkers as well as improving quality of life of affected patients. Overall, the aim to cure metastatic melanoma has become more tangible than ever before.

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Sinonasal, genital and acrolentiginous melanomas show distinct characteristics of KIT expression and mutations

Cited by 69 publications

References 40 publications

Unexpected Distribution of <b><i>cKIT</i></b> and <b><i>BRAF</i></b> Mutations among Southern Italian Patients with Sinonasal Melanoma

Unexpected Distribution of <b><i>cKIT</i></b> and <b><i>BRAF</i></b> Mutations among Southern Italian Patients with Sinonasal Melanoma

Treatment Algorithms in Stage IV Melanoma

Systemic Treatment of Melanoma

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