TERT and TERT promoter in melanocytic neoplasms: Current concepts in pathogenesis, diagnosis, and prognosis

Located on chromosome locus 5p15.33, telomerase reverse transcriptase (TERT or hTERT) encodes the catalytic subunit of telomerase which permits lengthening and preservation of telomeres following mitosis. Mutations in TERT promoter (TERT‐p) upregulate expression of TERT, allowing survival of malignant cells and tumor progression in wide variety of malignancies including melanoma. The objective of this review is to examine the roles of TERT and TERT‐p in the pathogenesis, diagnosis, and prognostication of cutaneous melanoma.

[1]  J. Pearson,et al.  Molecular Genomic Profiling of Melanocytic Nevi. , 2019, The Journal of investigative dermatology.

[2]  J. Parker,et al.  Utility of TERT Promoter Mutations for Cutaneous Primary Melanoma Diagnosis , 2019, The American Journal of dermatopathology.

[3]  Rajiv Kumar,et al.  TERT Promoter Mutations are Associated with Visceral Spreading in Melanoma of the Trunk , 2019, Cancers.

[4]  A. Haugh,et al.  The role of TERT promoter mutations in differentiating recurrent nevi from recurrent melanomas: A retrospective, case‐control study , 2019, Journal of the American Academy of Dermatology.

[5]  P. Kwok,et al.  Targeted genomic profiling of acral melanoma. , 2019, Journal of the National Cancer Institute.

[6]  D. Jukic,et al.  Concordance of somatic mutation profiles (BRAF,NRAS, and TERT) and tumoral PD-L1 in matched primary cutaneous and metastatic melanoma samples. , 2018, Human pathology.

[7]  Rajiv Kumar,et al.  TERT promoter mutation subtypes and survival in stage I and II melanoma patients , 2018, International journal of cancer.

[8]  J. Dai,et al.  TERT copy gain predicts the outcome of high-dose interferon α-2b therapy in acral melanoma , 2018, OncoTargets and therapy.

[9]  A. Ballestrero,et al.  Combining molecular and immunohistochemical analyses of key drivers in primary melanomas: interplay between germline and somatic variations , 2017, Oncotarget.

[10]  L. Akslen,et al.  Prognostic impact and concordance of TERT promoter mutation and protein expression in matched primary and metastatic cutaneous melanoma , 2017, British Journal of Cancer.

[11]  Rajiv Kumar,et al.  ETS1, nucleolar and non-nucleolar TERT expression in nevus to melanoma progression , 2017, Oncotarget.

[12]  Li Zhou,et al.  MAPK Pathway and TERT Promoter Gene Mutation Pattern and Its Prognostic Value in Melanoma Patients: A Retrospective Study of 2,793 Cases , 2017, Clinical Cancer Research.

[13]  J. Kirkwood,et al.  Genetic and Epigenetic Alterations of TERT Are Associated with Inferior Outcome in Adolescent and Young Adult Patients with Melanoma , 2017, Scientific Reports.

[14]  J. Becker,et al.  Distribution of TERT promoter mutations in primary and metastatic melanomas in Austrian patients , 2016, Journal of Cancer Research and Clinical Oncology.

[15]  D. Schadendorf,et al.  High TERT promoter mutation frequency in non‐acral cutaneous metastatic melanoma , 2016, Pigment cell & melanoma research.

[16]  Rajendra Singh,et al.  Frequency of telomerase reverse transcripter promoter mutations in desmoplastic melanoma subtypes: analyses of 76 cases , 2016, Melanoma research.

[17]  K. Hemminki,et al.  TERT promoter mutations in melanoma survival , 2019, Oncotarget.

[18]  J. Kirkwood,et al.  Association of TERT promoter mutations with telomerase expression in melanoma , 2016, Pigment cell & melanoma research.

[19]  R. Reis,et al.  Molecular profiling, including TERT promoter mutations, of acral lentiginous melanomas , 2016, Melanoma research.

[20]  Rajiv Kumar,et al.  TERT promoter mutations associate with fast‐growing melanoma , 2016, Pigment cell & melanoma research.

[21]  B. D. U. Bustos,et al.  Lack of TERT promoter mutations in melanomas with extensive regression. , 2016 .

[22]  J. Easton,et al.  The landscape of fusion transcripts in spitzoid melanoma and biologically indeterminate spitzoid tumors by RNA sequencing , 2016, Modern Pathology.

[23]  R. Dummer,et al.  The Genetic Evolution of Melanoma from Precursor Lesions. , 2015, The New England journal of medicine.

[24]  R. Dummer,et al.  Telomerase Expression by Aberrant Methylation of the TERT Promoter in Melanoma Arising in Giant Congenital Nevi , 2015, The Journal of investigative dermatology.

[25]  R. Dummer,et al.  TERT Promoter Mutations Are Predictive of Aggressive Clinical Behavior in Patients with Spitzoid Melanocytic Neoplasms , 2015, Scientific Reports.

[26]  G. Fontanini,et al.  Coexistence of TERT promoter and BRAF mutations in cutaneous melanoma is associated with more clinicopathological features of aggressiveness , 2015, Virchows Archiv.

[27]  J. Malvehy,et al.  TERT gene amplification is associated with poor outcome in acral lentiginous melanoma. , 2014, Journal of the American Academy of Dermatology.

[28]  Li Ding,et al.  The Genomic Landscape of Childhood and Adolescent Melanoma , 2014, The Journal of investigative dermatology.

[29]  D. Schadendorf,et al.  TERT promoter mutation status as an independent prognostic factor in cutaneous melanoma. , 2014, Journal of the National Cancer Institute.

[30]  M. Honavar,et al.  TERT promoter mutations in skin cancer: the effects of sun exposure and X-irradiation. , 2014, The Journal of investigative dermatology.

[31]  Y. Jeng,et al.  TERT promoter mutation is uncommon in acral lentiginous melanoma , 2014, Journal of cutaneous pathology.

[32]  Sandra Krüger,et al.  Melanomas of unknown primary frequently harbor TERT-promoter mutations , 2014, Melanoma research.

[33]  J. Malvehy,et al.  TERT and AURKA gene copy number gains enhance the detection of acral lentiginous melanomas by fluorescence in situ hybridization. , 2014, The Journal of molecular diagnostics : JMD.

[34]  J. Becker,et al.  Telomerase reverse transcriptase promoter mutations in primary cutaneous melanoma , 2014, Nature Communications.

[35]  Miguel Melo,et al.  Frequency of TERT promoter mutations in human cancers , 2013, Nature Communications.

[36]  D. Schadendorf,et al.  TERT Promoter Mutations in Familial and Sporadic Melanoma , 2013, Science.

[37]  J. Malvehy,et al.  Genetic alterations in RAS‐regulated pathway in acral lentiginous melanoma , 2013, Experimental dermatology.

[38]  G. Zamolo,et al.  Real-time expression of hTERT in primary melanoma biopsies. , 2010, Collegium antropologicum.

[39]  N. Polissar,et al.  Subclassification of desmoplastic melanoma: pure and mixed variants have significantly different capacities for lymph node metastasis , 2009, Journal of cutaneous pathology.

[40]  D. Coit,et al.  Cutaneous Desmoplastic Melanoma: Reappraisal of Morphologic Heterogeneity and Prognostic Factors , 2004, The American journal of surgical pathology.

[41]  L. Ben-Porat,et al.  Desmoplastic Melanoma: A Pathologically and Clinically Distinct Form of Cutaneous Melanoma , 2004, Annals of Surgical Oncology.

[42]  K. Peris,et al.  Heterogeneity of BRAF, NRAS, and TERT Promoter Mutational Status in Multiple Melanomas and Association with MC1R Genotype: Findings from Molecular and Immunohistochemical Analysis. , 2018, The Journal of molecular diagnostics : JMD.

[43]  H. Tsao,et al.  Telomerase reverse transcriptase (TERT) promoter mutations in Korean melanoma patients. , 2017, American journal of cancer research.