Longitudinal study of recurrent metastatic melanoma cell lines underscores the individuality of cancer biology. - Literature - Data resources

24270663

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

J Invest Dermatol, 2014/5;134(5):1389-1396.

Pos Z^[1], Spivey TL^[2], Liu H^[3], Sommariva M^[4], Chen J^[3], Wunderlich JR^[5], Parisi G^[6], Tomei S^[7], Ayotte BD^[8], Stroncek DF^[9], Malek JA^[7], Robbins PF^[5], Rivoltini L^[10], Maio M^[6], Chouchane L^[11], Wang E^[3], Marincola FM^[12]

Affiliations

Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA; Hungarian Academy of Sciences-Semmelweis University "Lendület" Experimental and Translational Immunomics Research Group, Budapest, Hungary; Department of Genetics, Cell, and Immunobiology, Semmelweis University, Budapest, Hungary.
Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA; Clinical Research Training Program (CRTP), National Institutes of Health, Bethesda, Maryland, USA; Department of General Surgery, Rush University Medical Center, Chicago, Illinois, USA.
Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA; Department of Biomedical Sciences for Health, Universita' degli Studi di Milano, Milan, Italy.
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Cancer Bioimmunotherapy Unit, Centro di Riferimento Oncologico, Aviano, Italy.
Department of Genetic Medicine, Weill Cornell Medical College in Qatar, Education City, Doha, Qatar.
Department of Biology, Northern Michigan University, Marquette, Michigan, USA.
Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Weill Cornell Medical College in Qatar, Education City, Doha, Qatar.
Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA; Research Branch, Sidra Medical and Research Centre, Doha, Qatar. Electronic address: fmarincola@sidra.org.

PMID: 24270663DOI: 10.1038/jid.2013.495

Impact factor: 7.59

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.

MeSH terms

Cell Line, Tumor; Comparative Genomic Hybridization; DNA Copy Number Variations; Disease Progression; Gene Deletion; Gene Expression Regulation, Neoplastic; Genomics; Humans; Longitudinal Studies; Melanoma; Neoplasm Recurrence, Local; Proto-Oncogene Mas; Skin Neoplasms; Transcriptome

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