Utility of TERT Promoter Mutations for Cutaneous Primary Melanoma Diagnosis

Nancy E. Thomas, Sharon N. Edmiston, Yihsuan S. Tsai, Joel S. Parker, Paul Googe, Klaus J. Busam, Glynis A. Scott, Daniel C. Zedek, Eloise A. Parrish, Honglin Hao, Nathaniel A. Slater, Michelle V. Pearlstein, Jill S. Frank, Pei Fen Kuan, David W. Ollila, Kathleen Conway

Research output: Contribution to journalArticle

Abstract

Telomerase reverse transcriptase (TERT) promoter mutations are commonly found in malignant melanomas but rare in melanocytic nevi. To assess its potential diagnostic utility for the distinction of melanoma from nevus, we determined the TERT promoter mutation status of 86 primary melanomas, 72 melanocytic nevi, and 40 diagnostically problematic melanocytic proliferations. Of the 86 melanomas, 67 (77.9%) were TERT-positive, defined as harboring a hotspot TERT promoter mutation at positions -124C>T, -124_125CC>TT, -138_139CC>TT, or -146C>T. Of the 72 nevi, only 1 (1.4%) was TERT-positive. Of the 40 diagnostically uncertain melanocytic proliferations, 2 (5.0%) were TERT-positive. TERT positivity as a test for melanoma versus nevus had an accuracy of 87.3% [95% confidence interval (CI), 81.1-92.1], a sensitivity of 77.9% (95% CI, 68.9-85.4), a specificity of 98.6% (95% CI, 95.8-100), a positive predictive value of 98.5% (95% CI, 95.6-100), and a negative predictive value of 78.9% (95% CI, 72.6-85.4). Our results indicate that hotspot TERT promoter mutation status may be a useful ancillary parameter for the diagnosis of melanoma. In particular, the high specificity of these mutations for melanoma indicates the presence of a TERT promoter mutation in a melanocytic neoplasm associated with diagnostic controversy, or uncertainty should increase concern for a melanoma.

Original languageEnglish (US)
Pages (from-to)264-272
Number of pages9
JournalThe American Journal of dermatopathology
Volume41
Issue number4
DOIs
StatePublished - Apr 1 2019

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Telomerase
Melanoma
Skin
Mutation
Confidence Intervals
Nevi and Melanomas
Pigmented Nevus
Nevus
Uncertainty

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Dermatology

Cite this

Thomas, N. E., Edmiston, S. N., Tsai, Y. S., Parker, J. S., Googe, P., Busam, K. J., ... Conway, K. (2019). Utility of TERT Promoter Mutations for Cutaneous Primary Melanoma Diagnosis. The American Journal of dermatopathology, 41(4), 264-272. https://doi.org/10.1097/DAD.0000000000001259

Utility of TERT Promoter Mutations for Cutaneous Primary Melanoma Diagnosis. / Thomas, Nancy E.; Edmiston, Sharon N.; Tsai, Yihsuan S.; Parker, Joel S.; Googe, Paul; Busam, Klaus J.; Scott, Glynis A.; Zedek, Daniel C.; Parrish, Eloise A.; Hao, Honglin; Slater, Nathaniel A.; Pearlstein, Michelle V.; Frank, Jill S.; Kuan, Pei Fen; Ollila, David W.; Conway, Kathleen.

In: The American Journal of dermatopathology, Vol. 41, No. 4, 01.04.2019, p. 264-272.

Research output: Contribution to journalArticle

Thomas, NE, Edmiston, SN, Tsai, YS, Parker, JS, Googe, P, Busam, KJ, Scott, GA, Zedek, DC, Parrish, EA, Hao, H, Slater, NA, Pearlstein, MV, Frank, JS, Kuan, PF, Ollila, DW & Conway, K 2019, 'Utility of TERT Promoter Mutations for Cutaneous Primary Melanoma Diagnosis' The American Journal of dermatopathology, vol. 41, no. 4, pp. 264-272. https://doi.org/10.1097/DAD.0000000000001259
Thomas, Nancy E. ; Edmiston, Sharon N. ; Tsai, Yihsuan S. ; Parker, Joel S. ; Googe, Paul ; Busam, Klaus J. ; Scott, Glynis A. ; Zedek, Daniel C. ; Parrish, Eloise A. ; Hao, Honglin ; Slater, Nathaniel A. ; Pearlstein, Michelle V. ; Frank, Jill S. ; Kuan, Pei Fen ; Ollila, David W. ; Conway, Kathleen. / Utility of TERT Promoter Mutations for Cutaneous Primary Melanoma Diagnosis. In: The American Journal of dermatopathology. 2019 ; Vol. 41, No. 4. pp. 264-272.
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abstract = "Telomerase reverse transcriptase (TERT) promoter mutations are commonly found in malignant melanomas but rare in melanocytic nevi. To assess its potential diagnostic utility for the distinction of melanoma from nevus, we determined the TERT promoter mutation status of 86 primary melanomas, 72 melanocytic nevi, and 40 diagnostically problematic melanocytic proliferations. Of the 86 melanomas, 67 (77.9{\%}) were TERT-positive, defined as harboring a hotspot TERT promoter mutation at positions -124C>T, -124_125CC>TT, -138_139CC>TT, or -146C>T. Of the 72 nevi, only 1 (1.4{\%}) was TERT-positive. Of the 40 diagnostically uncertain melanocytic proliferations, 2 (5.0{\%}) were TERT-positive. TERT positivity as a test for melanoma versus nevus had an accuracy of 87.3{\%} [95{\%} confidence interval (CI), 81.1-92.1], a sensitivity of 77.9{\%} (95{\%} CI, 68.9-85.4), a specificity of 98.6{\%} (95{\%} CI, 95.8-100), a positive predictive value of 98.5{\%} (95{\%} CI, 95.6-100), and a negative predictive value of 78.9{\%} (95{\%} CI, 72.6-85.4). Our results indicate that hotspot TERT promoter mutation status may be a useful ancillary parameter for the diagnosis of melanoma. In particular, the high specificity of these mutations for melanoma indicates the presence of a TERT promoter mutation in a melanocytic neoplasm associated with diagnostic controversy, or uncertainty should increase concern for a melanoma.",
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AU - Slater, Nathaniel A.

AU - Pearlstein, Michelle V.

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