Research Papers:

This article has been corrected. Correction in: Oncotarget. 2018; 9:28798.

Combining molecular and immunohistochemical analyses of key drivers in primary melanomas: interplay between germline and somatic variations

William Bruno _, Claudia Martinuzzi, Bruna Dalmasso, Virginia Andreotti, Lorenza Pastorino, Francesco Cabiddu, Marina Gualco, Francesco Spagnolo, Alberto Ballestrero, Paola Queirolo, Federica Grillo, Luca Mastracci and Paola Ghiorzo

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Oncotarget. 2018; 9:5691-5702. https://doi.org/10.18632/oncotarget.23204

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William Bruno1, Claudia Martinuzzi1, Bruna Dalmasso1, Virginia Andreotti1, Lorenza Pastorino1, Francesco Cabiddu2, Marina Gualco2, Francesco Spagnolo3, Alberto Ballestrero1, Paola Queirolo3, Federica Grillo4,*, Luca Mastracci4,* and Paola Ghiorzo1,*

1Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa and Ospedale Policlinico San Martino, Genoa, Italy

2Pathology Unit, Ospedale Policlinico San Martino, Genoa, Italy

3Department of Medical Oncology, Ospedale Policlinico San Martino, Genoa, Italy

4Department of Surgical and Diagnostic Sciences, Pathology Unit, University of Genoa and Ospedale Policlinico San Martino, Genoa, Italy

*These authors contributed equally to this work

Correspondence to:

William Bruno, email: [email protected]

Keywords: BRAF; primary melanoma; NRAS; CDKN2A; TERT

Received: September 01, 2017     Accepted: November 15, 2017     Published: December 14, 2017


Due to the high mutational somatic burden of Cutaneous Malignant Melanoma (CMM) a thorough profiling of the driver mutations and their interplay is necessary to explain the timing of tumorigenesis or for the identification of actionable genetic events. The aim of this study was to establish the mutation rate of some of the key drivers in melanoma tumorigenesis combining molecular analyses and/or immunohistochemistry in 93 primary CMMs from an Italian cohort also characterized for germline status, and to investigate an interplay between germline and somatic variants. BRAF mutations were present in 68% of cases, while CDKN2A germline mutations were found in 16 % and p16 loss in tissue was found in 63%. TERT promoter somatic mutations were detected in 38% of cases while the TERT –245T>C polymorphism was found in 51% of cases. NRAS mutations were found in 39% of BRAF negative or undetermined cases. NF1 was expressed in all cases analysed. MC1R variations were both considered as a dichotomous variable or scored. While a positive, although not significant association between CDKN2A germline mutations, but not MC1R variants, and BRAF somatic mutation was found, we did not observe other associations between germline and somatic events. A yet undescribed inverse correlation between TERT –245T>C polymorphism and the presence of BRAF mutation was found. It is possible to hypothesize that –245T>C polymorphism could be included in those genotypes which may influence the occurrence of BRAF mutations. Further studies are needed to investigate the role of –245T>C polymorphism as a germline predictor of BRAF somatic mutation status.

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