Longitudinal study of recurrent metastatic melanoma cell lines underscores the individuality of cancer biology

Zoltan Pos, Tara L. Spivey, Hui Liu, Michele Sommariva, Jinguo Chen, John R. Wunderlich, Giulia Parisi, Sara Tomei, Ben D. Ayotte, David F. Stroncek, Joel Malek, Paul F. Robbins, Licia Rivoltini, Michele Maio, Lotfi Chouchane, Ena Wang, Francesco M. Marincola

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Abstract

Recurrent metastatic melanoma provides a unique opportunity to analyze disease evolution in metastatic cancer. Here, we followed up eight patients with an unusually prolonged history of metastatic melanoma, who developed a total of 26 recurrences over several years. Cell lines derived from each metastasis were analyzed by comparative genomic hybridization and global transcript analysis. We observed that conserved, patient-specific characteristics remain stable in recurrent metastatic melanoma even after years and several recurrences. Differences among individual patients exceeded within-patient lesion variability, both at the DNA copy number (P<0.001) and RNA gene expression level (P<0.001). Conserved patient-specific traits included expression of several cancer/testis antigens and the c-kit proto-oncogene throughout multiple recurrences. Interestingly, subsequent recurrences of different patients did not display consistent or convergent changes toward a more aggressive disease phenotype. Finally, sequential recurrences of the same patient did not descend progressively from each other, as irreversible mutations such as homozygous deletions were frequently not inherited from previous metastases. This study suggests that the late evolution of metastatic melanoma, which markedly turns an indolent disease into a lethal phase, is prone to preserve case-specific traits over multiple recurrences and occurs through a series of random events that do not follow a consistent stepwise process.

Original languageEnglish
Pages (from-to)1389-1396
Number of pages8
JournalJournal of Investigative Dermatology
Volume134
Issue number5
DOIs
Publication statusPublished - 2014

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Pos, Z., Spivey, T. L., Liu, H., Sommariva, M., Chen, J., Wunderlich, J. R., Parisi, G., Tomei, S., Ayotte, B. D., Stroncek, D. F., Malek, J., Robbins, P. F., Rivoltini, L., Maio, M., Chouchane, L., Wang, E., & Marincola, F. M. (2014). Longitudinal study of recurrent metastatic melanoma cell lines underscores the individuality of cancer biology. Journal of Investigative Dermatology, 134(5), 1389-1396. https://doi.org/10.1038/jid.2013.495