Thin and thick primary cutaneous melanomas reveal distinct patterns of somatic copy number alterations
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Valentina Montagnani1,*, Matteo Benelli2,7,*, Alessandro Apollo1, Chiara Pescucci2, Danilo Licastro3, Carmelo Urso4, Gianni Gerlini5, Lorenzo Borgognoni5, Lucio Luzzatto1 and Barbara Stecca1,6
1 Core Research Laboratory, Istituto Toscano Tumori, Florence, Italy
2 Diagnostic Genetics Unit, Careggi University Hospital, Florence, Italy
3 CBM – Genomics, Area Science Park, Basovizza, Trieste, Italy
4 Anatomic Pathology Unit, Dermatopathology Section, S.M. Annunziata Hospital, Florence, Italy
5 Plastic Surgery Unit, S.M. Annunziata Hospital, Regional Melanoma Referral Center, Istituto Toscano Tumori, Florence, Italy
6 Department of Oncology, Careggi University Hospital, Florence, Italy
7 Center for Integrative Biology, University of Trento, Trento, Italy
* These authors have contributed equally to this work
Barbara Stecca, email:
Keywords: melanoma, somatic copy number alterations, exome sequencing
Received: February 09, 2016 Accepted: April 06, 2016 Published: April 15, 2016
Cutaneous melanoma is one of the most aggressive type of skin tumor. Early stage melanoma can be often cured by surgery; therefore current management guidelines dictate a different approach for thin (<1mm) versus thick (>4mm) melanomas. We have carried out whole-exome sequencing in 5 thin and 5 thick fresh-frozen primary cutaneous melanomas. Unsupervised hierarchical clustering analysis of somatic copy number alterations (SCNAs) identified two groups corresponding to thin and thick melanomas. The most striking difference between them was the much greater abundance of SCNAs in thick melanomas, whereas mutation frequency did not significantly change between the two groups. We found novel mutations and focal SCNAs in genes that are embryonic regulators of axon guidance, predominantly in thick melanomas. Analysis of publicly available microarray datasets provided further support for a potential role of Ephrin receptors in melanoma progression. In addition, we have identified a set of SCNAs, including amplification of BRAF and ofthe epigenetic modifier EZH2, that are specific for the group of thick melanomas that developed metastasis during the follow-up. Our data suggest that mutations occur early during melanoma development, whereas SCNAs might be involved in melanoma progression.
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