Familial Melanoma and Susceptibility Genes: A Review of the Most Common Clinical and Dermoscopic Phenotypic Aspect, Associated Malignancies and Practical Tips for Management
A family history of melanoma greatly increases the risk of developing cutaneous melanoma, a highly aggressive skin cancer whose incidence has been steadily increasing worldwide. Familial melanomas account for about 10% of all malignant melanomas and display an inheritance pattern consistent with the...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | Journal of Clinical Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0383/10/16/3760 |
| _version_ | 1797523366900400128 |
|---|---|
| author | Lamberto Zocchi Alberto Lontano Martina Merli Emi Dika Eduardo Nagore Pietro Quaglino Susana Puig Simone Ribero |
| author_facet | Lamberto Zocchi Alberto Lontano Martina Merli Emi Dika Eduardo Nagore Pietro Quaglino Susana Puig Simone Ribero |
| author_sort | Lamberto Zocchi |
| collection | DOAJ |
| description | A family history of melanoma greatly increases the risk of developing cutaneous melanoma, a highly aggressive skin cancer whose incidence has been steadily increasing worldwide. Familial melanomas account for about 10% of all malignant melanomas and display an inheritance pattern consistent with the presence of pathogenic germline mutations, among which those involving <i>CDKN2A</i> are the best characterized. In recent years, a growing number of genes, such as <i>MC1R</i>, <i>MITF</i>, <i>CDK4</i>, <i>POT1</i>, <i>TERT</i>, <i>ACD</i>, <i>TERF2IP</i>, and <i>BAP1</i>, have been implicated in familial melanoma. The fact that individuals harboring these germline mutations along with their close blood relatives have a higher risk of developing multiple primary melanomas as well as other internal organ malignancies, especially pancreatic cancer, makes cascade genetic testing and surveillance of these families of the utmost importance. Unfortunately, due to a polygenic inheritance mechanism involving multiple low-risk alleles, genetic modifiers, and environmental factors, it is still very difficult to predict the presence of these mutations. It is, however, known that germline mutation carriers can sometimes develop specific clinical traits, such as high atypical nevus counts and specific dermoscopic features, which could theoretically help clinicians predict the presence of these mutations in prone families. In this review, we provide a comprehensive overview of the high- and intermediate-penetrance genes primarily linked to familial melanoma, highlighting their most frequently associated non-cutaneous malignancies and clinical/dermoscopic phenotypes. |
| first_indexed | 2024-03-10T08:41:56Z |
| format | Article |
| id | doaj.art-65b77b3ff1b14bc1822e0ae06e5fe3e9 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T08:41:56Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-65b77b3ff1b14bc1822e0ae06e5fe3e92023-11-22T08:13:11ZengMDPI AGJournal of Clinical Medicine2077-03832021-08-011016376010.3390/jcm10163760Familial Melanoma and Susceptibility Genes: A Review of the Most Common Clinical and Dermoscopic Phenotypic Aspect, Associated Malignancies and Practical Tips for ManagementLamberto Zocchi0Alberto Lontano1Martina Merli2Emi Dika3Eduardo Nagore4Pietro Quaglino5Susana Puig6Simone Ribero7Department of Medical Sciences, Dermatology Clinic, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, Dermatology Clinic, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, Dermatology Clinic, University of Turin, 10126 Turin, ItalyDermatology, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, ItalyDepartment of Dermatology, Instituto Valenciano de Oncología, 46009 València, SpainDepartment of Medical Sciences, Dermatology Clinic, University of Turin, 10126 Turin, ItalyMelanoma Unit, Dermatology Department, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, 08001 Barcelona, SpainDepartment of Medical Sciences, Dermatology Clinic, University of Turin, 10126 Turin, ItalyA family history of melanoma greatly increases the risk of developing cutaneous melanoma, a highly aggressive skin cancer whose incidence has been steadily increasing worldwide. Familial melanomas account for about 10% of all malignant melanomas and display an inheritance pattern consistent with the presence of pathogenic germline mutations, among which those involving <i>CDKN2A</i> are the best characterized. In recent years, a growing number of genes, such as <i>MC1R</i>, <i>MITF</i>, <i>CDK4</i>, <i>POT1</i>, <i>TERT</i>, <i>ACD</i>, <i>TERF2IP</i>, and <i>BAP1</i>, have been implicated in familial melanoma. The fact that individuals harboring these germline mutations along with their close blood relatives have a higher risk of developing multiple primary melanomas as well as other internal organ malignancies, especially pancreatic cancer, makes cascade genetic testing and surveillance of these families of the utmost importance. Unfortunately, due to a polygenic inheritance mechanism involving multiple low-risk alleles, genetic modifiers, and environmental factors, it is still very difficult to predict the presence of these mutations. It is, however, known that germline mutation carriers can sometimes develop specific clinical traits, such as high atypical nevus counts and specific dermoscopic features, which could theoretically help clinicians predict the presence of these mutations in prone families. In this review, we provide a comprehensive overview of the high- and intermediate-penetrance genes primarily linked to familial melanoma, highlighting their most frequently associated non-cutaneous malignancies and clinical/dermoscopic phenotypes.https://www.mdpi.com/2077-0383/10/16/3760familial melanoma<i>CDKN2A</i><i>MC1R</i><i>MITF</i><i>CDK4</i><i>POT1</i> |
| spellingShingle | Lamberto Zocchi Alberto Lontano Martina Merli Emi Dika Eduardo Nagore Pietro Quaglino Susana Puig Simone Ribero Familial Melanoma and Susceptibility Genes: A Review of the Most Common Clinical and Dermoscopic Phenotypic Aspect, Associated Malignancies and Practical Tips for Management Journal of Clinical Medicine familial melanoma <i>CDKN2A</i> <i>MC1R</i> <i>MITF</i> <i>CDK4</i> <i>POT1</i> |
| title | Familial Melanoma and Susceptibility Genes: A Review of the Most Common Clinical and Dermoscopic Phenotypic Aspect, Associated Malignancies and Practical Tips for Management |
| title_full | Familial Melanoma and Susceptibility Genes: A Review of the Most Common Clinical and Dermoscopic Phenotypic Aspect, Associated Malignancies and Practical Tips for Management |
| title_fullStr | Familial Melanoma and Susceptibility Genes: A Review of the Most Common Clinical and Dermoscopic Phenotypic Aspect, Associated Malignancies and Practical Tips for Management |
| title_full_unstemmed | Familial Melanoma and Susceptibility Genes: A Review of the Most Common Clinical and Dermoscopic Phenotypic Aspect, Associated Malignancies and Practical Tips for Management |
| title_short | Familial Melanoma and Susceptibility Genes: A Review of the Most Common Clinical and Dermoscopic Phenotypic Aspect, Associated Malignancies and Practical Tips for Management |
| title_sort | familial melanoma and susceptibility genes a review of the most common clinical and dermoscopic phenotypic aspect associated malignancies and practical tips for management |
| topic | familial melanoma <i>CDKN2A</i> <i>MC1R</i> <i>MITF</i> <i>CDK4</i> <i>POT1</i> |
| url | https://www.mdpi.com/2077-0383/10/16/3760 |
| work_keys_str_mv | AT lambertozocchi familialmelanomaandsusceptibilitygenesareviewofthemostcommonclinicalanddermoscopicphenotypicaspectassociatedmalignanciesandpracticaltipsformanagement AT albertolontano familialmelanomaandsusceptibilitygenesareviewofthemostcommonclinicalanddermoscopicphenotypicaspectassociatedmalignanciesandpracticaltipsformanagement AT martinamerli familialmelanomaandsusceptibilitygenesareviewofthemostcommonclinicalanddermoscopicphenotypicaspectassociatedmalignanciesandpracticaltipsformanagement AT emidika familialmelanomaandsusceptibilitygenesareviewofthemostcommonclinicalanddermoscopicphenotypicaspectassociatedmalignanciesandpracticaltipsformanagement AT eduardonagore familialmelanomaandsusceptibilitygenesareviewofthemostcommonclinicalanddermoscopicphenotypicaspectassociatedmalignanciesandpracticaltipsformanagement AT pietroquaglino familialmelanomaandsusceptibilitygenesareviewofthemostcommonclinicalanddermoscopicphenotypicaspectassociatedmalignanciesandpracticaltipsformanagement AT susanapuig familialmelanomaandsusceptibilitygenesareviewofthemostcommonclinicalanddermoscopicphenotypicaspectassociatedmalignanciesandpracticaltipsformanagement AT simoneribero familialmelanomaandsusceptibilitygenesareviewofthemostcommonclinicalanddermoscopicphenotypicaspectassociatedmalignanciesandpracticaltipsformanagement |