Ultra-late melanoma recurrence is infrequent, poorly understood and, in most cases, difficult to unambiguously distinguish from a new primary melanoma. We identified a patient with a second melanoma diagnosed after a 30-year disease-free interval, and sought to determine if this new lesion was a recurrence of the original melanoma. Here we report the genomic sequence analysis of the exomes of 2 melanoma lesions isolated from the same individual in 1985 and 2015, and their comparison to each other and to the germline DNA of the patient. Identification of many shared somatic mutations between these lesions proves a lineal relationship spanning 30 years. Unlike prior reports of ultra-late melanoma recurrence, the availability of the original tumor and the use of comprehensive genomic analysis allowed us to confirm that the second lesion is truly a recurrence. We demonstrate the acquisition of numerous additional mutations during the 3 decade asymptomatic period. These data highlight the low but very long-lasting risk of recurrence in this patient population.

The rate of ultra-late recurrence (beyond 10-15 years) of cutaneous melanoma has been estimated to be between 2.0-6.9% from large case series. Two major factors complicate the interpretation of these data. Firstly, the risk of second primary melanoma is approximately 5% creating uncertainty about whether at least some of these late onset tumors might be independent of the original lesion. Secondly, in the majority of cases, the original pathology specimen is no longer available for comparative analysis. Accordingly, putative late recurrences are difficult to unambiguously distinguish from a new primary melanoma. We identified a patient with a second melanoma diagnosed after a 30 year disease-free interval, and sought to determine if this new lesion was a recurrence of the original melanoma. We report the genomic sequence analysis of the exomes of two melanoma lesions isolated from the same individual in 1985 and 2015, and their comparison to each other and to the germline DNA of the patient. Identification of many shared somatic mutations between these lesions prove a lineal relationship spanning 30 years. Unlike prior reports of ultra-late melanoma recurrence, the availability of the original tumor and the use of comprehensive genomic analysis allowed us to confirm that the second lesion is truly a recurrence. We demonstrate the acquisition of numerous additional mutations during the three decade asymptomatic period. This is, to our knowledge, the longest disease-free interval that has been rigorously confirmed in melanoma or any other solid tumor type. These data highlight the low but very long-lasting risk of recurrence in this patient population. Citation Format: Jerry J. Miller, Kristopher A. Lofgren, Sarah R. Hughes, Steven E. Cash, David R. Meier, Paraic A. Kenny. Genomic analysis of melanoma evolution following a 30 year disease-free interval [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3399. doi:10.1158/1538-7445.AM2017-3399