Genomic Rearrangements in Unusual and Atypical Melanocytic Neoplasms

Wiesner, Thomas

doi:10.1001/jamadermatol.2015.3501

Cited by 8 publications

(4 citation statements)

References 15 publications

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“…14,16,20,24,25 Since these discoveries, much has been learned about the pathogenesis of Spitz including the fact that a significant majority of Spitz, as well as some other classes of melanocytic neoplasms such as PRKCA fusion melanocytic nevi/ tumors, are the result of genomic fusions. 20,21,[33][34][35] However, there have been very few studies investigating whether fusions can play a role in agminated presentations of melanocytic neoplasms.…”

Section: Discussionmentioning

confidence: 99%

“…Since then, HRAS has also been recognized as a driver for nevus spilus and investigators have shown that while the entire nevus spilus carries an HRAS mutation, agminated Spitz arising in a nevus spilus also have copy number gains in 11p, where the HRAS gene resides 14,16,20,24,25 . Since these discoveries, much has been learned about the pathogenesis of Spitz including the fact that a significant majority of Spitz, as well as some other classes of melanocytic neoplasms such as PRKCA fusion melanocytic nevi/tumors, are the result of genomic fusions 20,21,33–35 . However, there have been very few studies investigating whether fusions can play a role in agminated presentations of melanocytic neoplasms.…”

Section: Discussionmentioning

confidence: 99%

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Agminated presentation of fusion‐driven melanocytic neoplasms

et al. 2023

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Background: The conventionally understood pathogenesis of agminated Spitz nevi includes a mosaic HRAS mutation followed by copy number gains in 11p. However, we have recently observed agminated presentations of fusion-driven melanocytic neoplasms.Methods: We retrieved cases from our database of benign fusion-induced melanocytic neoplasms with an agminated presentation. Both the primary lesion and the secondary lesion were sequenced. TERT-promoter mutational testing and the melanoma fluorescence in situ hybridization assay were also performed.Results: Three cases were included. Two had a PRKCA fusion (partners ATP2B4 and MPZL1) and one had a ZCCHC8::ROS1 fusion. None of the cases met morphologic or molecular criteria for malignancy. There was no evidence of tumor progression in secondary lesions. The same fusion was identified in the primary and secondary lesions. None of the patients developed evidence of nodal or systemic metastasis. Conclusions:We present accumulating evidence that fusion-driven melanocytic neoplasms can present with an agminated presentation. The differential diagnosis of an agminated presentation versus a locally recurrent or potentially locally metastatic tumor is critical, and accurate diagnosis has significant prognostic and therapeutic consequences for the patient. As with HRAS mutations, fusion-driven melanocytic tumors may have an agminated presentation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Agminated presentation of fusion‐driven melanocytic neoplasms

et al. 2023

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“…The fusion transcript-as with other kinase fusions described in melanocytic neoplasms-preserved the kinase domain of PRKCA but resulted in a loss the autoinhibitory domain, speculated to result in constitutive activity of the chimeric fusion protein. 16 The tumor bore considerable histologic similarity to the pigment-producing neoplasms termed pigmented epithelioid melanocytoma and the epithelioid blue nevi seen in Carney complex, a genodermatosis and cancer predisposition syndrome most often caused by a germline loss of function mutation in the tumor suppressor protein kinase A receptor subunit PRKAR1A. The authors suggested that Carney complex families lacking a PRKAR1A mutation may benefit from screening for PRKCA alterations.…”

Section: Prkca Fusionsmentioning

confidence: 99%

A review of kinase fusions in melanocytic tumors

Shalin

2017

Laboratory Investigation

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Translocations resulting in a kinase fusion are well reported in many tumor types and indeed can be defining, particularly in the case of hematopoietic malignancies. The recent reports of multiple protein kinase fusions within melanocytic neoplasms, particularly in those with spitzoid morphology, have heralded a new era of classification of these melanocytic tumors. Seen within approximately half of all spitzoid neoplasms and present within the full spectrum of benign, atypical, and malignant lesions, kinase fusions likely represent an early oncogenic event contributing to cell proliferation and growth. Although the presence of a kinase fusion does not seem to correlate with the biologic potential of a given lesion, documentation of a kinase fusion will likely be important, particularly in the case of spitzoid melanoma, as numerous specific kinase receptor inhibitors have shown promise as therapeutic agents in a subset of cases with kinase fusions. Interrogation of non-spitzoid melanomas for similar kinase fusions as a potential driving oncogenic mechanism has revealed some similarities and some differences. This review will focus on the kinase fusions described to date in spitzoid neoplasms and how subsequent studies have informed current melanoma research.

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“…6 Some authors have named such lesions ''melanocytic tumor of unknown malignant potential.'' 7,8 This correlation may be partially related to the fact that many molecular tests are constructed based on nonambiguous lesions in the first place. Cohort studies aimed at these specific types of lesions are needed.…”

mentioning

confidence: 99%

Molecular testing to differentiate melanoma from benign nevi: The gold standard limitation

Bitterman

2016

Journal of the American Academy of Dermatology

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Genomic Rearrangements in Unusual and Atypical Melanocytic Neoplasms

Cited by 8 publications

References 15 publications

Agminated presentation of fusion‐driven melanocytic neoplasms

Agminated presentation of fusion‐driven melanocytic neoplasms

A review of kinase fusions in melanocytic tumors

Molecular testing to differentiate melanoma from benign nevi: The gold standard limitation

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