Use of Targeted Next-Generation Sequencing to Identify Activating Hot Spot Mutations in Cherry Angiomas

Klebanov, Nikolai; Lin, William M.; Artomov, Mykyta; Shaughnessy, Michael F.; Njauw, Ching Ni; Bloom, Romi; Eterovic, Agda Karina; Chen, Ken; Kim, Tae Beom; Tsao, Sandy S

doi:10.1001/jamadermatol.2018.4231

Cited by 23 publications

(14 citation statements)

References 16 publications

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“…Multiple angiomas were significantly more frequent in patients with melanoma under 70 years old. Recently, one study has identified somatic activating mutations in GNAQ and GNA11 in a sample of cherry angiomas that also share uveal melanoma, blue nevus and melanoma associated with blue nevus 58 . In our study, the finding of cherry angiomas as a risk factor suggests that these lesions might be markers of actinic skin damage in patients with some degree of genetic susceptibility.…”

Section: Discussionsupporting

confidence: 58%

Risk factors for the development of a second melanoma in patients with cutaneous melanoma

Pastor‐Tomás

Martínez‐Franco

Bañuls

et al. 2020

Acad Dermatol Venereol

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Background Cutaneous melanoma patients have an increased risk of developing other neoplasms, especially cutaneous neoplasms and other melanomas. Identifying factors associated with an increased risk might be useful in the development of melanoma guidelines. Objectives To identify risk factors related to the development of a second primary melanoma in a series of patients diagnosed with sporadic melanoma and to establish the estimated incidence rate. Methods A longitudinal study based on prospective follow-up information of patients diagnosed with sporadic cutaneous melanoma at our centre from 2000 to 2015 was performed. Cumulative incidence was estimated based on competing risk models, and the association of characteristics with the risk of a second melanoma was performed by Cox proportional hazard models. Results Out of 1447 patients included in the study, after a median follow-up of 61 months, 55 patients (3.8%) developed a second melanoma. Fair hair colour, more than 100 common melanocytic nevi and the presence of more than 50 cherry angiomas were independently associated with the development of a second melanoma. The site and the histological subtype of the first and second melanomas were not consistent. The second melanomas were thinner than the first ones. Conclusions Fair-haired and multiple-nevi patients might benefit from more intensive prevention measures. The finding of cherry angiomas as a risk factor suggests that these lesions could be markers of skin sun damage in the setting of certain degree of genetic susceptibility.

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Section: Discussionsupporting

confidence: 58%

Risk factors for the development of a second melanoma in patients with cutaneous melanoma

Pastor‐Tomás

Martínez‐Franco

Bañuls

et al. 2020

Acad Dermatol Venereol

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“…Congenital hemangioma of the skin (RICH and NICH), which also cluster within this group, are an exception [10]. Other neoplasms that belong to this cluster are melanocytic tumors, specifically melanocytoma, nevus of the skin, blue nevus, choroidal nevus, choroidal melanoma, and vascular tumors like congenital hemangioma, hepatic small vessel neoplasia, anastomosing hemangioma, cherry angioma, and circumscribed choroidal hemangioma [9,10,12,13,14,15,16,17,18,29,30,31,32,33]. It is common for these tumors that make up this cluster to show continuous cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…GNAQ and its paralogue GNA11 each encode an alpha subunit of a heterotrimeric G protein, a binding protein that remains in its active GTP-bound state when mutated [7,8,9]. Both genes have been reported to be mutated in several vascular malformations such as congenital hemangioma of the skin and cherry angioma and in melanocytic tumors (choroidal nevus, uveal melanoma, melanocytoma, blue nevus) [6,9,10,11,12,13,14,15,16,17,18]. Moreover, GNAQ or GNA11 mutations have been detected in several neural crest disorders such as Sturge Weber Syndrome (SWS).…”

Section: Introductionmentioning

confidence: 99%

GNAQ Q209R Mutations Are Highly Specific for Circumscribed Choroidal Hemangioma

Guin

Metz²,

Kreis

et al. 2019

Cancers

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Several tumors, including uveal melanoma, show somatic mutations of GNAQ/GNA11. Circumscribed choroidal hemangioma is a benign tumor that becomes symptomatic in adulthood. In some patients, morphologic examination of biopsies is required for differential diagnosis between amelanotic choroidal melanoma and circumscribed choroidal hemangioma. Here, we report the results of GNAQ/GNA11 mutation analysis in samples from circumscribed choroidal hemangioma. Deep amplicon sequencing (Illumina MiSeq, San Diego, CA, USA) of positions R183 and Q209 of GNAQ and GNA11 in tissue samples from 33 patients with histologically diagnosed circumscribed choroidal hemangioma. All patients underwent biopsy or enucleation at our clinic between 2008 and 2018. To enable detection of variant alleles at low fractions, read depth exceeded 15,000-fold. DNA for genetic analysis was prepared from either snap-frozen (n = 22) or FFPE (n = 11) tissue samples. Samples from 28/33 patients (85%) showed a somatic missense mutation of GNAQ (c.626 A > G) predicted to result in p.Q209R. Variant allele fraction was variable (range 2.3% to 28%). Variants of GNAQ resulting in p.Q209 are characteristic for circumscribed choroidal hemangiomas. It appears that the GNAQ mutation spectrum in this tumor is narrow, possibly restricted to p.Q209R. Moreover, the spectrum is distinct from that of uveal melanoma, in which alterations resulting in p.Q209R are very rare.

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“…In particular, the association between MM and eruptive CAs, which we arbitrarily considered to be such when there were more than 10, was highly significant in patients younger than 70 years [2]. Interestingly, the results from subsequent studies, although very heterogeneous by methodology, design and objectives, seemed to support a likely association between CAs and tumours, namely breast cancer [3] and MM [4]. A recent study found that the presence of more than 50 CAs was significantly associated with an increased risk of developing a second MM in patients with cutaneous melanoma [5].…”

Section: Introductionmentioning

confidence: 99%

Eruptive Cherry Angiomas and Skin Melanoma: Further Insights into an Intriguing Association

et al. 2020

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Background: Some risk factors for malignant melanoma (MM) are recognized. Objective: To compare the strength of association between MM and eruptive cherry angiomas (CAs) with that of other well-known associations. Methods: This cross-sectional study included all subjects referred to the Outpatient Dermatology-Oncology and Dermoscopy Units of the Universities of Ferrara and Bologna, Italy, over a 5-month period and submitted to total body skin examination. We recorded: age, sex, cutaneous and non-cutaneous malignancies, presence of CAs, arbitrarily considered as “eruptive” when >10, >40 common melanocytic naevi or >2 clinically atypical naevi. The strength of association between the possible risk factors and MM was calculated by odds ratio in both the whole population and age quartiles. Variables associated with MM were included in multiple logistic regression analysis. Results: 1,190 subjects were included; 615 had malignant skin tumours, 462 MM, 85 extracutaneous tumours. Five hundred and eighty-seven subjects had eruptive CAs, 485 subjects >40 melanocytic naevi and 368 more than 2 atypical melanocytic naevi. Eruptive CAs, especially in subjects younger than 70, and >2 atypical melanocytic naevi, mostly in subjects older than 50, were significantly associated with MM. The strength of these 2 associations was similar. The presence of >40 melanocytic naevi was not associated with MM. Conclusions: These findings confirmed an association between MM and eruptive CAs, which was as strong as the one between MM and >2 atypical melanocytic naevi. CAs seem an intriguing model of interaction between heterogeneous variables, like immunocompetence, stimuli inducing endothelial cell proliferation, and oncogenesis, which deserves further investigation.

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Use of Targeted Next-Generation Sequencing to Identify Activating Hot Spot Mutations in Cherry Angiomas

Cited by 23 publications

References 16 publications

Risk factors for the development of a second melanoma in patients with cutaneous melanoma

Risk factors for the development of a second melanoma in patients with cutaneous melanoma

GNAQ Q209R Mutations Are Highly Specific for Circumscribed Choroidal Hemangioma

Eruptive Cherry Angiomas and Skin Melanoma: Further Insights into an Intriguing Association

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