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

Abstract

Recurrent metastatic melanoma provides a unique opportunity to analyze disease evolution in metastatic cancer. Here, we followed 8 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 dramatically 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 step-wise process.

A data-driven approach to improve wellness and reduce recurrence in cancer survivors

“…Finally, the data clouds from survivors who go on to develop recurrences, could offer insights into tumor evolution from a new point of view ( 67 ) and yield new insights into transitions to a state of cancer recurrence. As was true with the other wellness studies, it appears that malignant lesions of the same cancer type, from the same patient are more alike than those from different patients ( 67 ).…”

Quality Is King: Fundamental Insights into Tumor Antigenicity from Virus-Associated Merkel Cell Carcinoma

“…Primary resistance is generally a direct consequence of a patient's T cells being unable to respond to tumor, rendering ICB ineffective (Pos et al, 2014;Sharma et al, 2017). This may be driven by a number of factors: tumor lacking target antigen(s) (Gubin et al, 2014), dysfunctional antigen presentation (Marincola et al, 2000;Sucker et al, 2014), advanced or irreversible tumor-specific T-cell dysfunction, and/or lack of tumor-specific T cells.…”

Evolution of an intratumoral ecology susceptible to successive treatment in breast cancer xenografts

“…Comparison of recurrences, metastases, and primaries is similarly limited by the lack of information during the many months that often separate clinical samples [7][8][9].…”