Genetic Alterations in the INK4a/ARF Locus: Effects on Melanoma Development and Progression
Abstract
:1. Introduction
2. Somatic CDKN2A Alterations in Melanoma
3. Germline CDKN2A Alterations in Familial Melanoma
4. Functional Consequences of Melanoma-Associated CDKN2A Alterations
4.1. p16INK4a Mutations
4.2. p14ARF Mutations
5. Clinical Implications of CDKN2A: Impact on Response and Resistance to Current Treatments in Melanoma
5.1. MDM2 Inhibitors
5.2. CDK Inhibitors
5.3. Epigenetic Modulators
5.4. BRAF/MEK Inhibitors
5.5. Immune Checkpoint Inhibitors
5.6. Chemotherapy
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Molecular Subtype | BRAF (n = 188) | NRAS (n = 114) | NF1 (n = 66) | Triple Wild-Type (n = 45) |
---|---|---|---|---|
Mutations in p16INK4a only | 7.4% (14/188) | 6.1% (7/114) | 9.1% (6/66) | 0% (0/45) |
Mutations Affecting p16INK4a and p14ARF | 6.9% (13/188) | 7.9% (9/114) | 12.1% (8/66) | 4.4% (2/45) |
CDKN2A Deletions | 34.6% (65/188) | 30.7% (35/114) | 28.8% (19/66) | 17.8% (8/45) |
CDKN2A Hyper-Methylation | 67.0% (126/188) | 87.7% (100/114) | 77.3% (51/66) | 66.7% (30/45) |
Germline Mutations | CDKN2 ANM_000077.4 (p16INK4a) | CDKN2A NM_058195.3 (p14ARF) |
---|---|---|
Total Number of Coding Variants | 435 | 179 |
Number of Coding Variants | ||
Exon 1a | 140/435 (32%) | 0/477 (0%) |
Exon 1b | 0/435 (0% | 2/477 (0%) |
Exon 2 | 295/435 (68%) | 177/477 (37%) |
Exon 3 | 0/435 (0%) | 0/477 (0%) |
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Ming, Z.; Lim, S.Y.; Rizos, H. Genetic Alterations in the INK4a/ARF Locus: Effects on Melanoma Development and Progression. Biomolecules 2020, 10, 1447. https://doi.org/10.3390/biom10101447
Ming Z, Lim SY, Rizos H. Genetic Alterations in the INK4a/ARF Locus: Effects on Melanoma Development and Progression. Biomolecules. 2020; 10(10):1447. https://doi.org/10.3390/biom10101447
Chicago/Turabian StyleMing, Zizhen, Su Yin Lim, and Helen Rizos. 2020. "Genetic Alterations in the INK4a/ARF Locus: Effects on Melanoma Development and Progression" Biomolecules 10, no. 10: 1447. https://doi.org/10.3390/biom10101447