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Melanocytic Skin Neoplasms: What Lesson From Genomic Aberrations?
Am J Dermatopathol 2019; 41(9):623-629AJ

Abstract

Studies on the genomic aberrations in melanocytic neoplasms have shown a complex genomic landscape. In nevi and melanomas, a MAP-kinase pathway activation was generally found, produced by different chromosomal aberrations, including BRAF, NRAS, HRAS, GNAQ, GNA11, BAP1, CTNNB1, MAP2K1, PRKAR1A, and NF1 mutations, and ALK, ROS1, NTRK1, RET, MET, BRAF, NTRK3, and PRKCA fusions. Melanomas also showed a variable number of additional mutations ablating tumor-suppression mechanisms and activating other oncogenic pathways, including CDKN2A loss, PTEN loss, as well as TP53 and TERT-promoter mutations. Moreover, borderline melanocytic tumors displayed the same chromosomal aberrations, but more mutations than nevi and fewer than melanomas. In this context, the notion that melanocytic neoplasms can be classified as benign/malignant is hardly supportable, because all neoplasms harbor a certain number of mutations and the progression risk, that is, the malignant potential, is related and proportional to the burden of pathogenic mutations. Moreover, from the genomic analysis, in parallel to the current diagnostic categories of "nevi," "melanomas," and "melanocytomas," some aggregations or classes of tumors based on the characteristic types of driver mutations/fusions emerge as possible and more rationale, including Spitzoid neoplasms, blue neoplasms, BAP1-inactivated melanocytic neoplasms, deep penetrating melanocytic neoplasms, pigment-synthesizing melanocytic neoplasms, and "common" melanocytic neoplasms. Each of these classes, showing the same driver mutations/fusions, demonstrates to have the same pathogenesis and may be genetically considered as a single tumor, although with a variable amount of progression risk. Histologic features, being an expression of the mutational state, could be used to obtain an approximate risk assessment in each single tumor.

Authors+Show Affiliations

Scientific Director, Dermatopathology Study Center of Florence, Florence, Italy.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31433323

Citation

Urso, Carmelo. "Melanocytic Skin Neoplasms: what Lesson From Genomic Aberrations?" The American Journal of Dermatopathology, vol. 41, no. 9, 2019, pp. 623-629.
Urso C. Melanocytic Skin Neoplasms: What Lesson From Genomic Aberrations? Am J Dermatopathol. 2019;41(9):623-629.
Urso, C. (2019). Melanocytic Skin Neoplasms: What Lesson From Genomic Aberrations? The American Journal of Dermatopathology, 41(9), pp. 623-629. doi:10.1097/DAD.0000000000001341.
Urso C. Melanocytic Skin Neoplasms: what Lesson From Genomic Aberrations. Am J Dermatopathol. 2019;41(9):623-629. PubMed PMID: 31433323.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Melanocytic Skin Neoplasms: What Lesson From Genomic Aberrations? A1 - Urso,Carmelo, PY - 2019/8/22/entrez PY - 2019/8/23/pubmed PY - 2019/8/23/medline SP - 623 EP - 629 JF - The American Journal of dermatopathology JO - Am J Dermatopathol VL - 41 IS - 9 N2 - Studies on the genomic aberrations in melanocytic neoplasms have shown a complex genomic landscape. In nevi and melanomas, a MAP-kinase pathway activation was generally found, produced by different chromosomal aberrations, including BRAF, NRAS, HRAS, GNAQ, GNA11, BAP1, CTNNB1, MAP2K1, PRKAR1A, and NF1 mutations, and ALK, ROS1, NTRK1, RET, MET, BRAF, NTRK3, and PRKCA fusions. Melanomas also showed a variable number of additional mutations ablating tumor-suppression mechanisms and activating other oncogenic pathways, including CDKN2A loss, PTEN loss, as well as TP53 and TERT-promoter mutations. Moreover, borderline melanocytic tumors displayed the same chromosomal aberrations, but more mutations than nevi and fewer than melanomas. In this context, the notion that melanocytic neoplasms can be classified as benign/malignant is hardly supportable, because all neoplasms harbor a certain number of mutations and the progression risk, that is, the malignant potential, is related and proportional to the burden of pathogenic mutations. Moreover, from the genomic analysis, in parallel to the current diagnostic categories of "nevi," "melanomas," and "melanocytomas," some aggregations or classes of tumors based on the characteristic types of driver mutations/fusions emerge as possible and more rationale, including Spitzoid neoplasms, blue neoplasms, BAP1-inactivated melanocytic neoplasms, deep penetrating melanocytic neoplasms, pigment-synthesizing melanocytic neoplasms, and "common" melanocytic neoplasms. Each of these classes, showing the same driver mutations/fusions, demonstrates to have the same pathogenesis and may be genetically considered as a single tumor, although with a variable amount of progression risk. Histologic features, being an expression of the mutational state, could be used to obtain an approximate risk assessment in each single tumor. SN - 1533-0311 UR - https://www.unboundmedicine.com/medline/citation/31433323/Melanocytic_Skin_Neoplasms:_What_Lesson_From_Genomic_Aberrations L2 - http://dx.doi.org/10.1097/DAD.0000000000001341 DB - PRIME DP - Unbound Medicine ER -