Genetic Variants and Somatic Alterations Associated with MITF-E318K Germline Mutation in Melanoma Patients
| Autor: | Lorenza Di Guardo, Andrea C. Ferrari, Monica Rodolfo, Licia Rivoltini, Loris De Cecco, Simona Frigerio, Siranoush Manoukian, Gianfrancesco Gallino, Erika Feltrin, Mara Cossa, Andrea Devecchi, Marialuisa Sensi, Elisabetta Vergani, Viviana Vallacchi, Bernard Peissel, Andrea Maurichi, Matteo Dugo |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Proto-Oncogene Proteins B-raf Heterozygote Skin Neoplasms Biology QH426-470 Germline MITF gene Young Adult cutaneous melanoma Germline mutation CDKN2A Exome Sequencing Genetic predisposition medicine Genetics Humans MITF-E318K variant Melanoma neoplasms Cyclin-Dependent Kinase Inhibitor p16 Germ-Line Mutation Genetics (clinical) Exome sequencing Aged Aged 80 and over Microphthalmia-Associated Transcription Factor MTAP gene integumentary system copy number alterations Communication Middle Aged medicine.disease Cutaneous melanoma Chromosomal region Cancer research SKCM-TCGA Pan Cancer Atlas germline mutations somatic mutations Female Chromosomes Human Pair 9 Receptor Melanocortin Type 1 |
| Zdroj: | Genes, Vol 12, Iss 1440, p 1440 (2021) Genes |
| ISSN: | 2073-4425 |
| Popis: | The MITF-E318K variant has been implicated in genetic predisposition to cutaneous melanoma. We addressed the occurrence of MITF-E318K and its association with germline status of CDKN2A and MC1R genes in a hospital-based series of 248 melanoma patients including cohorts of multiple, familial, pediatric, sporadic and melanoma associated with other tumors. Seven MITF-E318K carriers were identified, spanning every group except the pediatric patients. Three carriers showed mutated CDKN2A, five displayed MC1R variants, while the sporadic carrier revealed no variants. Germline/tumor whole exome sequencing for this carrier revealed germline variants of unknown significance in ATM and FANCI genes and, in four BRAF-V600E metastases, somatic loss of the MITF wild-type allele, amplification of MITF-E318K and deletion of a 9p21.3 chromosomal region including CDKN2A and MTAP. In silico analysis of tumors from MITF-E318K melanoma carriers in the TCGA Pan-Cancer-Atlas dataset confirmed the association with BRAF mutation and 9p21.3 deletion revealing a common genetic pattern. MTAP was the gene deleted at homozygous level in the highest number of patients. These results support the utility of both germline and tumor genome analysis to define tumor groups providing enhanced information for clinical strategies and highlight the importance of melanoma prevention programs for MITF-E318K patients. |
| Databáze: | OpenAIRE |
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