A Single Center Retrospective Review of Patients from Central Italy Tested for Melanoma Predisposition Genes.
Adult
Aged
Cyclin-Dependent Kinase 4
/ genetics
Cyclin-Dependent Kinase Inhibitor p16
/ genetics
Female
Genetic Predisposition to Disease
/ genetics
Humans
Italy
Male
Melanoma
/ genetics
Microphthalmia-Associated Transcription Factor
/ genetics
Middle Aged
Retrospective Studies
Shelterin Complex
Telomere-Binding Proteins
/ genetics
Tumor Suppressor Proteins
/ genetics
Ubiquitin Thiolesterase
/ genetics
familial melanoma
melanoma susceptibility genes
multiple primary melanoma
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
11 Dec 2020
11 Dec 2020
Historique:
received:
06
11
2020
revised:
26
11
2020
accepted:
09
12
2020
entrez:
16
12
2020
pubmed:
17
12
2020
medline:
16
3
2021
Statut:
epublish
Résumé
Cutaneous malignant melanoma (CMM) is one of the most common skin cancers worldwide. CMM pathogenesis involves genetic and environmental factors. Recent studies have led to the identification of new genes involved in CMM susceptibility: beyond CDKN2A and CDK4, BAP1, POT1, and MITF were recently identified as potential high-risk melanoma susceptibility genes. This study is aimed to evaluate the genetic predisposition to CMM in patients from central Italy. From 1998 to 2017, genetic testing was performed in 888 cases with multiple primary melanoma and/or familial melanoma. Genetic analyses included the sequencing CDKN2A, CDK4, BAP1, POT1, and MITF in 202 cases, and of only CDKN2A and CDK4 codon 24 in 686 patients. By the evaluation of the personal and familial history, patients were divided in two clinical categories: "low significance" and "high significance" cases. 128 patients (72% belonging to the "high significance" category, 28% belonging to the "low significance" category) were found to carry a DNA change defined as pathogenic, likely pathogenic, variant of unknown significance (VUS)-favoring pathogenic or VUS. It is important to verify the genetic predisposition in CMM patients for an early diagnosis of further melanomas and/or other tumors associated with the characterized genotype.
Sections du résumé
BACKGROUND
BACKGROUND
Cutaneous malignant melanoma (CMM) is one of the most common skin cancers worldwide. CMM pathogenesis involves genetic and environmental factors. Recent studies have led to the identification of new genes involved in CMM susceptibility: beyond CDKN2A and CDK4, BAP1, POT1, and MITF were recently identified as potential high-risk melanoma susceptibility genes.
OBJECTIVE
OBJECTIVE
This study is aimed to evaluate the genetic predisposition to CMM in patients from central Italy.
METHODS
METHODS
From 1998 to 2017, genetic testing was performed in 888 cases with multiple primary melanoma and/or familial melanoma. Genetic analyses included the sequencing CDKN2A, CDK4, BAP1, POT1, and MITF in 202 cases, and of only CDKN2A and CDK4 codon 24 in 686 patients. By the evaluation of the personal and familial history, patients were divided in two clinical categories: "low significance" and "high significance" cases.
RESULTS
RESULTS
128 patients (72% belonging to the "high significance" category, 28% belonging to the "low significance" category) were found to carry a DNA change defined as pathogenic, likely pathogenic, variant of unknown significance (VUS)-favoring pathogenic or VUS.
CONCLUSIONS
CONCLUSIONS
It is important to verify the genetic predisposition in CMM patients for an early diagnosis of further melanomas and/or other tumors associated with the characterized genotype.
Identifiants
pubmed: 33322357
pii: ijms21249432
doi: 10.3390/ijms21249432
pmc: PMC7763813
pii:
doi:
Substances chimiques
BAP1 protein, human
0
CDKN2A protein, human
0
Cyclin-Dependent Kinase Inhibitor p16
0
Microphthalmia-Associated Transcription Factor
0
POT1 protein, human
0
Shelterin Complex
0
Telomere-Binding Proteins
0
Tumor Suppressor Proteins
0
Cyclin-Dependent Kinase 4
EC 2.7.11.22
Ubiquitin Thiolesterase
EC 3.4.19.12
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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