Longitudinal Study of Recurrent Metastatic Melanoma Cell Lines Underscores the Individuality of Cancer Biology View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-05

AUTHORS

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 A Malek, Paul F Robbins, Licia Rivoltini, Michele Maio, Lotfi Chouchane, Ena Wang, Francesco M Marincola

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. More... »

PAGES

1389-1396

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/jid.2013.495

DOI

http://dx.doi.org/10.1038/jid.2013.495

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1024214049

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24270663


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