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Germline and somatic mutations in patients with multiple primary melanomas: a next generation sequencing study
Milena Casula1, Panagiotis Paliogiannis2, Fabrizio Ayala3
1Unit of Cancer Genetics, Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), Traversa La Crucca 3, Baldinca Li Punti, 07100, Sassari, Italy.
BMC Cancer
|August 7, 2019
Summary
CDKN2A mutations are key in Italian multiple primary melanomas (MPM), especially with family history. Genetic analysis reveals varied mutations across populations, highlighting heterogeneity in sporadic MPM and driver mutations.
Area of Science:
- Oncology
- Genetics
- Dermatology
Background:
- Multiple primary melanomas (MPM) affect up to 8% of cutaneous malignant melanoma (CMM) patients.
- While often sporadic with somatic mutations, familial cases linked to CDKN2A germline mutations exist in Caucasian populations.
Purpose of the Study:
- To investigate the incidence, distribution, and impact of germline and somatic mutations in Italian MPM patients.
- To identify genetic factors contributing to MPM development in an Italian cohort.
Main Methods:
- Genomic DNA analysis using next-generation sequencing on peripheral blood (germline) and tissue samples (somatic).
- Utilized a specific multi-gene panel for somatic analysis and a commercial cancer hotspot panel.
- Enrolled 102 MPM patients for germline analysis and 5 patients with at least four MPMs for somatic analysis.
Main Results:
- CDKN2A mutations found in 37.5% of MPM cases with a family history versus 3.5% without.
- Identified MC1R, ATM, and BAP1 variants, with BAP1 variants specific to southern Italy.
- Frequent somatic variants included BRAF, TP53, KIT, PIK3CA, KDR, and NRAS.
Conclusions:
- CDKN2A mutations are significant susceptibility factors in Italian MPM, particularly with a family history.
- Mutation prevalence varies among Italian subpopulations, indicating genetic heterogeneity.
- Observed heterogeneity in driver somatic mutations and other sequence variants requires further clinical impact elucidation.
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