Lack of association between CDKN2A germline mutations and survival in patients with melanoma: A retrospective cohort study
Authors: Norbertus Anton Ipenburg, Mary-Ann El Sharouni, Remco van Doorn, Paul J. van Diest, Monique E. van Leerdam, Jasper I. van der Rhee, Jelle Goeman, Nicole A. Kukutsch, Dyon G.C.T.M. Snels, Sybren Dekker, Robert L. van Leeuwen, Tondo van Rijssen, Erik Honig, Jacqueline Vink, Marianne B. Crijns, Ineke Bruynzeel, Francis P.K. Wu, Biljana Zupan-Kajcovski, Jacqueline Schuur
Journal: Journal of the American Academy of Dermatology (2021)

To the Editor: Approximately 10% of patients with cutaneous melanomas have a positive melanoma family history. Germline mutation of the CDKN2A gene is the most common cause of familial melanoma.1Read J. Wadt K.A.W. Hayward N.K. Melanoma genetics.J Med Genet. 2016; 53: 1-14https://doi.org/10.1136/jmedgenet-2015-103150Crossref PubMed Scopus (133) Google Scholar Mutation carriers have a lifetime risk of melanoma of approximately 70%, and many patients develop melanoma at a younger age.2van der Rhee J.I. Krijnen P. Gruis N.A. et al.Clinical and histologic characteristics of malignant melanoma in families with a germline mutation in CDKN2A.J Am Acad Dermatol. 2011; 65: 281-288https://doi.org/10.1016/j.jaad.2010.06.044Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar For other cancer types, there is evidence that patients with hereditary tumors have different prognoses than patients with sporadic tumors. However, it is uncertain whether CDKN2A mutation carriership (CDKN2A-mut) affects melanoma prognosis.3Helgadottir H. Höiom V. Tuominen R. et al.Germline CDKN2A mutation status and survival in familial melanoma cases.J Natl Cancer Inst. 2016; 108: djw135https://doi.org/10.1093/jnci/djw135Crossref Scopus (30) Google Scholar, 4Helgadottir H. Tuominen R. Olsson H. Hansson J. Höiom V. Cancer risks and survival in patients with multiple primary melanomas: association with family history of melanoma and germline CDKN2A mutation status.J Am Acad Dermatol. 2017; 77: 893-901https://doi.org/10.1016/j.jaad.2017.05.050Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar, 5Dalmasso B. Pastorino L. Ciccarese G. et al.CDKN2A germline mutations are not associated with poor survival in an Italian cohort of melanoma patients.J Am Acad Dermatol. 2019; 80: 1263-1271https://doi.org/10.1016/j.jaad.2018.07.060Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar The aim of this study was to compare the survival of CDKN2A-mut patients with that of patients with sporadic melanoma.All adults newly diagnosed with invasive, clinically localized, primary cutaneous melanoma between January 1, 2000, and December 31, 2014, were included. Data of 89 CDKN2A-mut patients were extracted from the database of the Netherlands Foundation for Detection of Hereditary Tumors. A population-based cohort of 56,929 patients with sporadic melanoma was extracted from PALGA (the Dutch Nationwide Network and Registry of Histopathology and Cytopathology) and the Netherlands Cancer Registry. Ethical approval was granted by the ethical review boards of PALGA and Leiden University Medical Center . Cox proportional hazards regression analyses were performed. See the Supplementary Text (available via Mendeley at https://doi.org/10.17632/h4m4zwdysx.1) for all statistical analyses.CDKN2A-mut patients more often developed multiple primary melanomas (MPMs) than patients with sporadic melanoma (42.7% vs 4.0%; P < .0001). The median age at diagnosis of the first melanoma was 15 years lower for CDKN2A-mut patients than for patients with sporadic melanoma (42 vs 57 years; P < .0001). CDKN2A-mut patients had thinner melanomas (median Breslow thickness, 0.6 mm vs 0.9 mm; P < .0001) (Table I). After correcting for gender, Breslow thickness, age at diagnosis of first melanoma, primary site, ulceration, sentinel node status, melanoma subtype, and year of diagnosis, overall survival (OS) and recurrence-free survival (RFS) were not significantly different for patients with and without germline CDKN2A mutations (OS hazard ratio [HR], 1.44; 95% CI, 0.85-2.43; RFS HR, 0.91; 95% CI, 0.45-1.83) (Table II).Table IBaseline characteristics of CDKN2A germline mutation–positive and sporadic melanoma patientsCharacteristicsCDKN2A-mut (N = 89)Sporadic (N = 56,929)P valueGender, n (%).13 Female57 (64.0)31,916 (56.1) Male32 (36.0)25,013 (43.9)Median age at diagnosis of first melanoma, y (IQR)42 (31-50)57 (44-68)<.0001Year of diagnosis<.0001 2000/200115 (16.9)4928 (8.7) 2002/200317 (19.1)5459 (9.6) 2004/200513 (14.6)6396 (11.2) 2006/200715 (16.9)6979 (12.3) 2008/200910 (11.2)810 (14.2) 2010/201111 (12.4)9308 (16.4) 2012/2013/20148 (9.0)15,759 (27.7)Primary site, n (%).04 Head and neck5 (5.6)7127 (12.5) Trunk35 (39.3)23,892 (42.0) Upper limb18 (20.2)8327 (14.6) Lower limb31 (34.8)15,725 (27.6) Not known0 (0.0)1858 (3.3)Median Breslow thickness, mm (IQR)0.6 (0.4-0.9)0.9 (0.5-1.8)<.0001Breslow thickness, mm, n (%)<.0001 <0.853 (60.9)23,270 (40.9) ≤0.8-1.016 (18.4)9311 (16.4) 1.1-2.015 (17.2)12,614 (22.2) 2.1-4.03 (3.4)7668 (13.5) >4.00 (0.0)4066 (7.1)Subtype, n (%).03 Nonnodular84 (94.4)49,248 (86.5) Nodular5 (5.6)7679 (13.5)Ulceration, n (%)<.0001 No53 (59.6)39,030 (68.6) Yes1 (1.1)7587 (13.3) Unknown35 (39.3)10,312 (18.1)Mitoses, n (%).05 No14 (15.7)9914 (17.4) Yes29 (32.6)12,522 (22.0) Unknown46 (51.7)34,493 (60.6)Multiple melanoma<.0001 No (SPM)51 (57.3)54,645 (96.0) Yes (MPM)38 (42.7)2284 (4.0)SN status, n (%).50 Negative7 (87.5)9162 (77.5) Positive1 (12.5)2666 (22.5) Not performed8145,099Median follow-up, y (IQR)11.5 (9.4-15.7)6.3 (3.6-10.3)<.0001CDKN2A-mut, CDKN2A germline mutation-positive melanoma patients; IQR, interquartile range; MPM, multiple primary melanoma; SN, sentinel node; SPM, single primary melanoma. Open table in a new tab Table IIUni- and multivariable Cox regression for overall survival and recurrence-free survival for all patients (N = 51,921)VariableClassOverall survival (10,457 events)Recurrence-free survival (6865 events)UnivariableMultivariableUnivariableMultivariableHR (95% CI)P valueHR (95% CI)P valueHR (95% CI)P valueHR (95% CI)P valueCDKN2ANot mutated1111Mutated0.52 (0.31-0.88).011.44 (0.85-2.43).180.48 (0.24-0.98).040.91 (0.45-1.83).78GenderMale1111Female0.58 (0.55-0.60)<.00010.69 (0.66-0.72)<.00010.59 (0.57-0.63)<.00010.72 (0.68-0.75)<.0001Breslow thicknessPer mm1.11 (1.10-1.11)<.00011.06 (1.06-1.07)<.00011.11 (1.11-1.11)<.00011.08 (1.08-1.09)<.0001Age at diagnosis of first melanoma18-27111128-370.16 (0.94-1.45).171.14 (0.91-1.41).260.98 (0.82-1.16).801.00 (0.84-1.19).9938-471.67 (1.36-2.05)<.00011.61 (1.31-1.97)<.00011.19 (1.01-1.40).041.24 (1.05-1.46).0148-572.54 (2.08-3.09)<.00012.30 (1.89-2.82)<.00011.54 (1.31-1.81)<.00011.43 (1.21-1.68)<.000158-674.32 (3.55-5.26)<.00013.66 (3.01-4.47)<.00011.90 (1.62-2.22)<.00011.66 (1.42-1.95)<.000168-778.49 (6.98-10.33)<.00017.00 (5.75-8.53)<.00012.30 (1.96-2.69)<.00011.83 (1.56-2.15)<.000178-8719.55 (16.07-23.79)<.000114.94 (12.25-18.22)<.00012.86 (2.42-3.38)<.00012.02 (1.71-2.40)<.000188+45.53 (37.03-55.97)<.000129.22 (23.65-36.10)<.00013.44 (2.74-4.31)<.00011.49 (1.17-1.91).001Primary siteHead and neck1111Trunk0.53 (0.50-0.55)<.00010.95 (0.90-1.01).090.77 (0.71-0.82)<.00010.88 (0.82-0.95).001Upper limb0.52 (0.48-0.55)<.00010.78 (0.73-0.83)<.00010.52 (0.48-.58)<.00010.61 (0.55-0.67)<.0001Lower limb0.46 (0.43-0.48)<.00010.83 (0.78-0.88)<.00010.81 (0.76-0.88)<.00011.01 (0.93-1.09).83UlcerationNo1111Yes4.25 (4.08-4.42)<.00012.18 (2.08-2.28)<.00015.42 (5.16-5.69)<.00012.97 (2.81-3.14)<.0001SN statusNegative1111Positive2.87 (2.64-3.11)<.00012.42 (2.23-2.63)<.00013.20 (2.95-3.47)<.00012.39 (2.20-2.60)<.0001Not performed1.21 (1.15-1.28)<.00011.15 (1.09-1.22)<.00010.71 (0.66-0.75)<.00010.96 (0.90-1.02).17SubtypeNonnodular1111Nodular2.83 (2.71-2.95)<.00011.41 (1.34-1.48)<.00013.61 (3.43-3.80)<.00011.80 (1.70-1.91)<.0001Year of diagnosis2000/200111112002/20030.94 (0.88-1.01).120.87 (0.81-0.94)<.00010.92 (0.84-1.01).090.84 (0.76-0.93)<.00012004/20050.93 (0.86-0.99).030.87 (0.81-0.94)<.00010.93 (0.85-1.02).110.89 (0.81-0.98).022006/20070.99 (0.92-1.06).680.93 (0.87-1.01).070.98 (0.89-1.07).610.98 (0.89-1.07).642008/20090.93 (0.87-1.01).070.82 (0.76-0.88)<.00010.85 (0.78-0.94).0010.85 (0.77-0.93).0012010/20110.94 (0.87-1.02).120.79 (0.73-0.86)<.00010.89 (0.81-0.98).010.88 (0.80-0.97).0072012/2013/20140.91 (0.84-0.98).010.71 (0.65-0.76)<.00010.94 (0.86-1.02).150.91 (0.83-0.99).04HR, Hazard ratio; SN, sentinel node. Open table in a new tab Our finding that CDKN2A mutation status is not associated with worse OS or RFS is in line with that of an Italian cohort study.5Dalmasso B. Pastorino L. Ciccarese G. et al.CDKN2A germline mutations are not associated with poor survival in an Italian cohort of melanoma patients.J Am Acad Dermatol. 2019; 80: 1263-1271https://doi.org/10.1016/j.jaad.2018.07.060Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar In contrast, 2 Swedish studies showed worse survival for CDKN2A-mut patients.3Helgadottir H. Höiom V. Tuominen R. et al.Germline CDKN2A mutation status and survival in familial melanoma cases.J Natl Cancer Inst. 2016; 108: djw135https://doi.org/10.1093/jnci/djw135Crossref Scopus (30) Google Scholar,4Helgadottir H. Tuominen R. Olsson H. Hansson J. Höiom V. Cancer risks and survival in patients with multiple primary melanomas: association with family history of melanoma and germline CDKN2A mutation status.J Am Acad Dermatol. 2017; 77: 893-901https://doi.org/10.1016/j.jaad.2017.05.050Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar The aims and design of the studies differed. We used a nationwide control group of almost 60,000 patients, which made it possible to control for multiple confounders. Previous studies did not control for primary site, ulceration, melanoma subtype, or sentinel node status.3Helgadottir H. Höiom V. Tuominen R. et al.Germline CDKN2A mutation status and survival in familial melanoma cases.J Natl Cancer Inst. 2016; 108: djw135https://doi.org/10.1093/jnci/djw135Crossref Scopus (30) Google Scholar,5Dalmasso B. Pastorino L. Ciccarese G. et al.CDKN2A germline mutations are not associated with poor survival in an Italian cohort of melanoma patients.J Am Acad Dermatol. 2019; 80: 1263-1271https://doi.org/10.1016/j.jaad.2018.07.060Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar In 1 study, only MPM patients were included.4Helgadottir H. Tuominen R. Olsson H. Hansson J. Höiom V. Cancer risks and survival in patients with multiple primary melanomas: association with family history of melanoma and germline CDKN2A mutation status.J Am Acad Dermatol. 2017; 77: 893-901https://doi.org/10.1016/j.jaad.2017.05.050Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar OS was assessed in all 4 studies, while in our study, RFS was studied instead of melanoma-specific survival.3Helgadottir H. Höiom V. Tuominen R. et al.Germline CDKN2A mutation status and survival in familial melanoma cases.J Natl Cancer Inst. 2016; 108: djw135https://doi.org/10.1093/jnci/djw135Crossref Scopus (30) Google Scholar, 4Helgadottir H. Tuominen R. Olsson H. Hansson J. Höiom V. Cancer risks and survival in patients with multiple primary melanomas: association with family history of melanoma and germline CDKN2A mutation status.J Am Acad Dermatol. 2017; 77: 893-901https://doi.org/10.1016/j.jaad.2017.05.050Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar, 5Dalmasso B. Pastorino L. Ciccarese G. et al.CDKN2A germline mutations are not associated with poor survival in an Italian cohort of melanoma patients.J Am Acad Dermatol. 2019; 80: 1263-1271https://doi.org/10.1016/j.jaad.2018.07.060Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar In accordance with earlier studies, CDKN2A-mut patients were younger at diagnosis and more prone to developing MPM.2van der Rhee J.I. Krijnen P. Gruis N.A. et al.Clinical and histologic characteristics of malignant melanoma in families with a germline mutation in CDKN2A.J Am Acad Dermatol. 2011; 65: 281-288https://doi.org/10.1016/j.jaad.2010.06.044Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar,3Helgadottir H. Höiom V. Tuominen R. et al.Germline CDKN2A mutation status and survival in familial melanoma cases.J Natl Cancer Inst. 2016; 108: djw135https://doi.org/10.1093/jnci/djw135Crossref Scopus (30) Google Scholar,5Dalmasso B. Pastorino L. Ciccarese G. et al.CDKN2A germline mutations are not associated with poor survival in an Italian cohort of melanoma patients.J Am Acad Dermatol. 2019; 80: 1263-1271https://doi.org/10.1016/j.jaad.2018.07.060Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Close surveillance of CDKN2A-mut patients is probably one of the reasons why melanomas of CDKN2A-mut patients were diagnosed at less advanced stages. The retrospective design, a relatively small number of CDKN2A-mut patients, missing melanoma-specific survival, ascertainment bias, and longevity bias are limitations of this study.In conclusion, the presence of germline CDKN2A mutation was not associated with melanoma survival in the present study. To the Editor: Approximately 10% of patients with cutaneous melanomas have a positive melanoma family history. Germline mutation of the CDKN2A gene is the most common cause of familial melanoma.1Read J. Wadt K.A.W. Hayward N.K. Melanoma genetics.J Med Genet. 2016; 53: 1-14https://doi.org/10.1136/jmedgenet-2015-103150Crossref PubMed Scopus (133) Google Scholar Mutation carriers have a lifetime risk of melanoma of approximately 70%, and many patients develop melanoma at a younger age.2van der Rhee J.I. Krijnen P. Gruis N.A. et al.Clinical and histologic characteristics of malignant melanoma in families with a germline mutation in CDKN2A.J Am Acad Dermatol. 2011; 65: 281-288https://doi.org/10.1016/j.jaad.2010.06.044Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar For other cancer types, there is evidence that patients with hereditary tumors have different prognoses than patients with sporadic tumors. However, it is uncertain whether CDKN2A mutation carriership (CDKN2A-mut) affects melanoma prognosis.3Helgadottir H. Höiom V. Tuominen R. et al.Germline CDKN2A mutation status and survival in familial melanoma cases.J Natl Cancer Inst. 2016; 108: djw135https://doi.org/10.1093/jnci/djw135Crossref Scopus (30) Google Scholar, 4Helgadottir H. Tuominen R. Olsson H. Hansson J. Höiom V. Cancer risks and survival in patients with multiple primary melanomas: association with family history of melanoma and germline CDKN2A mutation status.J Am Acad Dermatol. 2017; 77: 893-901https://doi.org/10.1016/j.jaad.2017.05.050Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar, 5Dalmasso B. Pastorino L. Ciccarese G. et al.CDKN2A germline mutations are not associated with poor survival in an Italian cohort of melanoma patients.J Am Acad Dermatol. 2019; 80: 1263-1271https://doi.org/10.1016/j.jaad.2018.07.060Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar The aim of this study was to compare the survival of CDKN2A-mut patients with that of patients with sporadic melanoma. All adults newly diagnosed with invasive, clinically localized, primary cutaneous melanoma between January 1, 2000, and December 31, 2014, were included. Data of 89 CDKN2A-mut patients were extracted from the database of the Netherlands Foundation for Detection of Hereditary Tumors. A population-based cohort of 56,929 patients with sporadic melanoma was extracted from PALGA (the Dutch Nationwide Network and Registry of Histopathology and Cytopathology) and the Netherlands Cancer Registry. Ethical approval was granted by the ethical review boards of PALGA and Leiden University Medical Center . Cox proportional hazards regression analyses were performed. See the Supplementary Text (available via Mendeley at https://doi.org/10.17632/h4m4zwdysx.1) for all statistical analyses. CDKN2A-mut patients more often developed multiple primary melanomas (MPMs) than patients with sporadic melanoma (42.7% vs 4.0%; P < .0001). The median age at diagnosis of the first melanoma was 15 years lower for CDKN2A-mut patients than for patients with sporadic melanoma (42 vs 57 years; P < .0001). CDKN2A-mut patients had thinner melanomas (median Breslow thickness, 0.6 mm vs 0.9 mm; P < .0001) (Table I). After correcting for gender, Breslow thickness, age at diagnosis of first melanoma, primary site, ulceration, sentinel node status, melanoma subtype, and year of diagnosis, overall survival (OS) and recurrence-free survival (RFS) were not significantly different for patients with and without germline CDKN2A mutations (OS hazard ratio [HR], 1.44; 95% CI, 0.85-2.43; RFS HR, 0.91; 95% CI, 0.45-1.83) (Table II). CDKN2A-mut, CDKN2A germline mutation-positive melanoma patients; IQR, interquartile range; MPM, multiple primary melanoma; SN, sentinel node; SPM, single primary melanoma. HR, Hazard ratio; SN, sentinel node. Our finding that CDKN2A mutation status is not associated with worse OS or RFS is in line with that of an Italian cohort study.5Dalmasso B. Pastorino L. Ciccarese G. et al.CDKN2A germline mutations are not associated with poor survival in an Italian cohort of melanoma patients.J Am Acad Dermatol. 2019; 80: 1263-1271https://doi.org/10.1016/j.jaad.2018.07.060Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar In contrast, 2 Swedish studies showed worse survival for CDKN2A-mut patients.3Helgadottir H. Höiom V. Tuominen R. et al.Germline CDKN2A mutation status and survival in familial melanoma cases.J Natl Cancer Inst. 2016; 108: djw135https://doi.org/10.1093/jnci/djw135Crossref Scopus (30) Google Scholar,4Helgadottir H. Tuominen R. Olsson H. Hansson J. Höiom V. Cancer risks and survival in patients with multiple primary melanomas: association with family history of melanoma and germline CDKN2A mutation status.J Am Acad Dermatol. 2017; 77: 893-901https://doi.org/10.1016/j.jaad.2017.05.050Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar The aims and design of the studies differed. We used a nationwide control group of almost 60,000 patients, which made it possible to control for multiple confounders. Previous studies did not control for primary site, ulceration, melanoma subtype, or sentinel node status.3Helgadottir H. Höiom V. Tuominen R. et al.Germline CDKN2A mutation status and survival in familial melanoma cases.J Natl Cancer Inst. 2016; 108: djw135https://doi.org/10.1093/jnci/djw135Crossref Scopus (30) Google Scholar,5Dalmasso B. Pastorino L. Ciccarese G. et al.CDKN2A germline mutations are not associated with poor survival in an Italian cohort of melanoma patients.J Am Acad Dermatol. 2019; 80: 1263-1271https://doi.org/10.1016/j.jaad.2018.07.060Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar In 1 study, only MPM patients were included.4Helgadottir H. Tuominen R. Olsson H. Hansson J. Höiom V. Cancer risks and survival in patients with multiple primary melanomas: association with family history of melanoma and germline CDKN2A mutation status.J Am Acad Dermatol. 2017; 77: 893-901https://doi.org/10.1016/j.jaad.2017.05.050Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar OS was assessed in all 4 studies, while in our study, RFS was studied instead of melanoma-specific survival.3Helgadottir H. Höiom V. Tuominen R. et al.Germline CDKN2A mutation status and survival in familial melanoma cases.J Natl Cancer Inst. 2016; 108: djw135https://doi.org/10.1093/jnci/djw135Crossref Scopus (30) Google Scholar, 4Helgadottir H. Tuominen R. Olsson H. Hansson J. Höiom V. Cancer risks and survival in patients with multiple primary melanomas: association with family history of melanoma and germline CDKN2A mutation status.J Am Acad Dermatol. 2017; 77: 893-901https://doi.org/10.1016/j.jaad.2017.05.050Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar, 5Dalmasso B. Pastorino L. Ciccarese G. et al.CDKN2A germline mutations are not associated with poor survival in an Italian cohort of melanoma patients.J Am Acad Dermatol. 2019; 80: 1263-1271https://doi.org/10.1016/j.jaad.2018.07.060Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar In accordance with earlier studies, CDKN2A-mut patients were younger at diagnosis and more prone to developing MPM.2van der Rhee J.I. Krijnen P. Gruis N.A. et al.Clinical and histologic characteristics of malignant melanoma in families with a germline mutation in CDKN2A.J Am Acad Dermatol. 2011; 65: 281-288https://doi.org/10.1016/j.jaad.2010.06.044Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar,3Helgadottir H. Höiom V. Tuominen R. et al.Germline CDKN2A mutation status and survival in familial melanoma cases.J Natl Cancer Inst. 2016; 108: djw135https://doi.org/10.1093/jnci/djw135Crossref Scopus (30) Google Scholar,5Dalmasso B. Pastorino L. Ciccarese G. et al.CDKN2A germline mutations are not associated with poor survival in an Italian cohort of melanoma patients.J Am Acad Dermatol. 2019; 80: 1263-1271https://doi.org/10.1016/j.jaad.2018.07.060Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Close surveillance of CDKN2A-mut patients is probably one of the reasons why melanomas of CDKN2A-mut patients were diagnosed at less advanced stages. The retrospective design, a relatively small number of CDKN2A-mut patients, missing melanoma-specific survival, ascertainment bias, and longevity bias are limitations of this study. In conclusion, the presence of germline CDKN2A mutation was not associated with melanoma survival in the present study. None disclosed.