KIT, NRAS, BRAF and PTEN mutations in a sample of Swedish patients with acral lentiginous melanoma

Zebary, Abdlsattar; Omholt, Katarina; Vassilaki, Ismini; Höiom, Veronica; Lindén, Diana; Viberg, Lisa; Kanter‐Lewensohn, Lena; Johansson, Carolina; Hansson, Johan

doi:10.1016/j.jdermsci.2013.07.013

Cited by 87 publications

(96 citation statements)

References 196 publications

(283 reference statements)

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“…In a European study investigating 5 and 6 cases, rates were 0% (ALM) and 17% (mucosal melanoma), respectively [5]. A Swedish study found 17% of BRAF mutations in 88 cases of ALM [32]. Interestingly, we saw higher BRAF mutation rates in ALM and slightly lower rates in mucosal melanoma.…”

Section: Discussionmentioning

confidence: 48%

Pathogenetic Implications of BRAF Mutation Distribution in Stage IV Melanoma Patients

Baiter

Hartmann²,

Schneider‐Stock³

et al. 2015

Dermatology

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Background: BRAF mutation frequencies in melanoma subtypes have clinical implications and offer pathogenetic clues. Objectives: To characterize BRAF mutation status in melanoma of unknown primary (MUP) patients, in histological melanoma subtypes and by localization of primary tumors. Methods: In 179 patients with stage IV metastatic melanoma, BRAF mutation status, histological subtype and localization of primary (except for 29 MUP patients) were analyzed. Results: BRAF mutations were found in 44.3%, of which 80.5% were BRAF V600E and 19.5% showed non-V600E BRAF mutations. BRAF mutation frequency depended on histological subtype (57.4% superficial spreading melanoma, 54.7% nodular melanoma, 11.1% mucosal melanoma, 28.6% acral lentiginous melanoma) and concerning non-V600E BRAF mutations on localization of primary. In MUP the BRAF mutation pattern resembled superficial spreading and nodular melanomas. Conclusion: BRAF mutation frequencies depend on histological subtype and localization of primary melanoma. Non-V600E BRAF mutations mostly occur in patients with primaries on ‘head and neck' as well as ‘trunk' but not on ‘extremities'.

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Section: Discussionmentioning

confidence: 48%

Pathogenetic Implications of BRAF Mutation Distribution in Stage IV Melanoma Patients

Baiter

Hartmann²,

Schneider‐Stock³

et al. 2015

Dermatology

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“…In a recent study from our group, we found that SNMM has a low frequency of BRAF, NRAS and KIT mutations [11], known driver mutations for cutaneous, vulvar and acral melanomas [12][13][14][15][16][17][18]. This indicates that SNMMs harbour other unknown underlying oncogenic driver mutations.…”

Section: Introductionmentioning

confidence: 92%

TERT promoter mutations in sinonasal malignant melanoma

Jangard

Zebary²,

Ragnarsson-Olding³

et al. 2015

Melanoma Research

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Sinonasal malignant melanoma (SNMM) comprises less than 1% of all melanomas and is located in the nasal cavity and the paranasal sinuses. The majority of SNMMs have unknown underlying oncogenic driver mutations. The recent identification of a high frequency of driver mutations in the promoter of the telomerase reverse transcriptase (TERT) gene in cutaneous melanoma led us to investigate whether these mutations also occur in SNMM. Our aim was to determine the TERT promoter mutation frequencies in primary SNMMs. Laser capture microdissection and manual dissection were used to isolate tumour cells from 49 formalin-fixed paraffin-embedded tissues. The tumours were screened for TERT promoter mutations by direct Sanger sequencing. Information on NRAS, BRAF and KIT mutation was available from an earlier study. Overall, 8% (4/49) of SNMMs harboured TERT promoter mutations. One of these mutated tumours had a coexistent NRAS mutation and one had a BRAF mutation. Our findings show that TERT promoter mutations are present in a moderate proportion of SNMM. No conclusion can be drawn on their potential influence on the clinical outcome or tumour progression.

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“…Gain-of-function BRAF mutations are common in melanoma, and although patients with tumors harboring mutant BRAF initially respond to targeted agents, resistance develops in most cases (Wiesner et al, 2012;Zebary et al, 2013;Boussemart et al, 2014). Significant efforts have been made to understand the sensitivity and resistance to vemurafenib in this context, with several investigations focusing on the ERK and phosphatidylinositol 3 0 -kinase -Akt/mTOR pathways in melanoma progression (Nazarian et al, 2010;Villanueva et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

The Role of eIF4E in Response and Acquired Resistance to Vemurafenib in Melanoma

Yao

Dahabieh

Rajakumar

et al. 2015

Journal of Investigative Dermatology

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In eukaryotic cells, the rate-limiting component for cap-dependent mRNA translation is the translation initiation factor eIF4E. eIF4E is overexpressed in a variety of human malignancies, but whether it has a role in melanoma remains obscure. We hypothesized that eIF4E promotes melanoma cell proliferation and facilitates the development of acquired resistance to the BRAF inhibitor vemurafenib. We show that eIF4E is overexpressed in a panel of melanoma cell lines, compared with immortalized melanocytes. Knockdown of eIF4E significantly repressed the proliferation of a subset of melanoma cell lines. Moreover, in BRAF(V600E) melanoma cell lines, vemurafenib inhibits 4E-BP1 phosphorylation, thus promoting its binding to eIF4E. Cap-binding and polysome profiling analysis confirmed that vemurafenib stabilizes the eIF4E-4E-BP1 association and blocks mRNA translation, respectively. Conversely, in cells with acquired resistance to vemurafenib, there is an increased dependence on eIF4E for survival; 4E-BP1 is highly phosphorylated and thus eIF4E-4E-BP1 associations are impeded. Moreover, increasing eIF4E activity by silencing 4E-BP1/2 renders vemurafenib-responsive cells more resistant to BRAF inhibition. In conclusion, these data suggest that therapeutically targeting eIF4E may be a viable means of inhibiting melanoma cell proliferation and overcoming vemurafenib resistance.

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KIT, NRAS, BRAF and PTEN mutations in a sample of Swedish patients with acral lentiginous melanoma

Cited by 87 publications

References 196 publications

Pathogenetic Implications of BRAF Mutation Distribution in Stage IV Melanoma Patients

Pathogenetic Implications of BRAF Mutation Distribution in Stage IV Melanoma Patients

TERT promoter mutations in sinonasal malignant melanoma

The Role of eIF4E in Response and Acquired Resistance to Vemurafenib in Melanoma

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