Simona De Summa1, Antonia Lasorella1, Sabino Strippoli2, Giuseppe Giudice3, Gabriella Guida4, Rossella Elia3, Eleonora Nacchiero3, Amalia Azzariti5, Nicola Silvestris6,7, Michele Guida2, Stefania Guida8, Stefania Tommasi1, Rosamaria Pinto1. 1. Pharmacogenetics and Molecular Diagnostic Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy. 2. Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy. 3. Department of Plastic and Reconstructive Surgery, University of Bari, Bari, Italy. 4. Department of Basic Medical Science and Sense Organs, University of Bari, Bari, Italy. 5. Pharmacology Laboratory IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy. 6. Medical Oncology Unit IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy. 7. Biomedical Sciences and Human Oncology (DIMO), University of Bari "Aldo Moro", Bari, Italy. 8. Dermatology Unit, Department of Surgical, Medical, Dental and Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.
Abstract
Background: Melanoma has a complex molecular background and multiple genes are involved in its development and progression. The advent of next generation sequencing platforms has enabled the evaluation of multiple genes at a time, thus unraveling new insights into the genetics of melanoma. We investigated a set of germline mutations able to discriminate the development of multiple primary melanomas (MPM) vs. single site primary melanomas (SPM) using a targeted next generation sequencing panel. Materials and Methods: A total of 39 patients, 20 with SPM and 19 with MPM, were enrolled in our study. Next generation analysis was carried out using a custom targeted sequencing panel that included 32 genes known to have a role in several carcinogenic pathways, such as those involved in DNA repair, pigmentation, regulation of kinases, cell cycle control and senescence. Results: We found a significant correlation between PIK3CA:p.I391M and MPMs, compared to SPMs, p = 0.031 and a trend for the association between CYP1B1: p.N453S and SPMs, compared to MPMs (p = 0.096). We also found that both subgroups shared a spectrum of 9 alterations in 8 genes (CYP1B1: p.N453S, BAP1: p.C39fs, PIK3CA: p.I391M, CDKAL1: c.1226_1227TG, POLE: p.V1161fs, OCA2: p.R419Q, OCA2: p.R305W, MC1R: p.V60L, MGMT: p.L115F), which suggested that these genes may play a role in melanoma development. Conclusions: In conclusion, despite the small cohort of patients, we found that germline mutations, such as those of PIK3CAand CYP1B1, might contribute to the differential development of SPM and MPM.
Background: Melanoma has a complex molecular background and multiple genes are involved in its development and progression. The advent of next generation sequencing platforms has enabled the evaluation of multiple genes at a time, thus unraveling new insights into the genetics of melanoma. We investigated a set of germline mutations able to discriminate the development of multiple primary melanomas (MPM) vs. single site primary melanomas (SPM) using a targeted next generation sequencing panel. Materials and Methods: A total of 39 patients, 20 with SPM and 19 with MPM, were enrolled in our study. Next generation analysis was carried out using a custom targeted sequencing panel that included 32 genes known to have a role in several carcinogenic pathways, such as those involved in DNA repair, pigmentation, regulation of kinases, cell cycle control and senescence. Results: We found a significant correlation between PIK3CA:p.I391M and MPMs, compared to SPMs, p = 0.031 and a trend for the association between CYP1B1: p.N453S and SPMs, compared to MPMs (p = 0.096). We also found that both subgroups shared a spectrum of 9 alterations in 8 genes (CYP1B1: p.N453S, BAP1: p.C39fs, PIK3CA: p.I391M, CDKAL1: c.1226_1227TG, POLE: p.V1161fs, OCA2: p.R419Q, OCA2: p.R305W, MC1R: p.V60L, MGMT: p.L115F), which suggested that these genes may play a role in melanoma development. Conclusions: In conclusion, despite the small cohort of patients, we found that germline mutations, such as those of PIK3CAand CYP1B1, might contribute to the differential development of SPM and MPM.
Authors: Rodolfo David Palacios-Diaz; Blanca de Unamuno-Bustos; Carlos Abril-Pérez; Mónica Pozuelo-Ruiz; Javier Sánchez-Arraez; Ignacio Torres-Navarro; Rafael Botella-Estrada Journal: J Clin Med Date: 2022-04-22 Impact factor: 4.964