Genetic and morphologic features for melanoma classification

Broekaert, Sigrid M. C.; Roy, Ritu; Okamoto, Ichiro; Oord, Joost van den; Bauer, Jürgen; Garbe, Claus; Barnhill, Raymond L.; Busam, Klaus J.; Cochran, Alistair J.; Cook, Martin; Elder, David E.; McCarthy, Stanley W.; Mihm, Martín C.; Schadendorf, Dirk; Scolyer, Richard A.; Spatz, Alan; Bastian, Boris C.

doi:10.1111/j.1755-148x.2010.00778.x

Cited by 138 publications

(157 citation statements)

References 19 publications

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“…Some studies have shown that this mutation is prevalent in younger patients (Goel et al, 2006;Liu et al, 2007;Broekaert et al, 2010;Hacher et al, 2010;Menzies et al, 2011;Long et al, 2011). However, this association was not confirmed in the metaanalysis by Lee et al (2011) or in the present study.…”

Section: Discussioncontrasting

confidence: 56%

Analysis of the BRAF V600E mutation in primary cutaneous melanoma

Inumaru¹,

Gordo²,

Junior

et al. 2014

Genet. Mol. Res.

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ABSTRACT. BRAF V600E is the most common mutation in cutaneous melanomas, and has been described in 30-72% of such cases. This mutation results in the substitution of valine for glutamic acid at position 600 of the BRAF protein, which consequently becomes constitutively activated. The present study investigated the BRAF V600E mutation frequency and its clinical implications in a group of 77 primary cutaneous melanoma patients treated in a cancer reference center in Brazil. Mutation analysis 2841 BRAF V600E mutation of primary cutaneous melanomas in Brazil ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (2): 2840-2848 (2014) was accomplished by polymerase chain reaction, restriction fragment length polymorphism, and automated DNA sequencing. The chi-squared and Fischer exact tests were used for comparative analyses. The BRAF V600E mutation was detected in 54/77 (70.1%) melanoma subjects. However, no statistically significant association was found between the presence of the mutation and clinical or prognostic parameters. Our results demonstrated that the BRAF V600E mutation is a common event in melanomas, representing an important molecular target for novel therapeutic approaches in such tumors.

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Section: Discussioncontrasting

confidence: 56%

Analysis of the BRAF V600E mutation in primary cutaneous melanoma

Inumaru¹,

Gordo²,

Junior

et al. 2014

Genet. Mol. Res.

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“…BRAF-mutant melanoma is associated with younger patient age, lack of CSD at the primary site, truncal location, high body nevus counts, and certain pathologic characteristics (12,13,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Just as BRAF wild-type and mutant melanoma have differing clinicopathologic features, we hypothesized that the mutant genotypes are also distinct.…”

Section: Introductionmentioning

confidence: 99%

Distinguishing Clinicopathologic Features of Patients with V600E and V600K BRAF-Mutant Metastatic Melanoma

Menzies

Haydu

Visintin

et al. 2012

Clinical Cancer Research

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Purpose: Certain clinicopathologic features correlate with BRAF mutation status in melanoma including younger age and primary subtype. This study sought to determine the BRAF mutation status by age-decade and whether BRAF-mutant genotypes correlated with clinicopathologic features and outcome in patients with metastatic melanoma.Methods: A prospectively assembled cohort of Australian patients were followed from diagnosis of metastatic melanoma (N ¼ 308). Clinicopathologic variables were correlated with BRAF mutational status, genotype, and survival.Results: Forty-six percent of patients had a BRAF mutation; 73% V600E, 19% V600K, and 8% other genotypes. An inverse relationship existed between BRAF mutation prevalence and age-decade (P < 0.001). All patients <30 years and only 25% 70 years had BRAF-mutant melanoma. Amongst BRAF-mutant melanoma, the frequency of non-V600E genotypes (including V600K) increased with increasing age. Non-V600E genotypes comprised <20% in patients <50 years and >40% in those 70 years. A higher degree of cumulative sun-induced damage correlated with V600K but not V600E melanoma (P ¼ 0.002). The diseasefree interval from diagnosis of primary melanoma to first distant metastasis was shorter for patients with V600K compared with V600E melanoma (17.4 vs. 39.2 months, P ¼ 0.048), with no difference in survival thereafter. In patients BRAF tested at diagnosis of metastatic melanoma, one year survival from diagnosis of metastasis was significantly longer for patients with BRAF-mutant melanoma treated with an inhibitor (83%), than those not treated with an inhibitor (29%, P < 0.001), or patients with BRAF wild-type melanoma (37%, P < 0.001).Conclusion: Different genotypes exist within BRAF-mutant metastatic melanoma, representing biologically and clinically discrete subtypes, suggesting distinct etiology and behavior.

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“…Many aggressive melanomas, including BRAF V600E melanomas, maintain differentiation characteristics in situ (Broekaert et al, 2010;Ohsie et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Differentiated melanocyte cell division occurs in vivo and is promoted by mutations in Mitf

Taylor

Lister

Zeng³

et al. 2011

Development

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SUMMARYCoordination of cell proliferation and differentiation is crucial for tissue formation, repair and regeneration. Some tissues, such as skin and blood, depend on differentiation of a pluripotent stem cell population, whereas others depend on the division of differentiated cells. In development and in the hair follicle, pigmented melanocytes are derived from undifferentiated precursor cells or stem cells. However, differentiated melanocytes may also have proliferative capacity in animals, and the potential for differentiated melanocyte cell division in development and regeneration remains largely unexplored. Here, we use time-lapse imaging of the developing zebrafish to show that while most melanocytes arise from undifferentiated precursor cells, an unexpected subpopulation of differentiated melanocytes arises by cell division. Depletion of the overall melanocyte population triggers a regeneration phase in which differentiated melanocyte division is significantly enhanced, particularly in young differentiated melanocytes. Additionally, we find reduced levels of Mitf activity using an mitfa temperature-sensitive line results in a dramatic increase in differentiated melanocyte cell division. This supports models that in addition to promoting differentiation, Mitf also promotes withdrawal from the cell cycle. We suggest differentiated cell division is relevant to melanoma progression because the human melanoma mutation MITF 4T⌬2B promotes increased and serial differentiated melanocyte division in zebrafish. These results reveal a novel pathway of differentiated melanocyte division in vivo, and that Mitf activity is essential for maintaining cell cycle arrest in differentiated melanocytes.

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Genetic and morphologic features for melanoma classification

Cited by 138 publications

References 19 publications

Analysis of the BRAF V600E mutation in primary cutaneous melanoma

Analysis of the BRAF V600E mutation in primary cutaneous melanoma

Distinguishing Clinicopathologic Features of Patients with V600E and V600K BRAF-Mutant Metastatic Melanoma

Differentiated melanocyte cell division occurs in vivo and is promoted by mutations in Mitf

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