American Association for Cancer Research
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Supplementary Figure S2 from CD271 Expression on Patient Melanoma Cells Is Unstable and Unlinked to Tumorigenicity

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posted on 2023-03-30, 23:20 authored by Samantha E. Boyle, Clare G. Fedele, Vincent Corbin, Elisha Wybacz, Pacman Szeto, Jeremy Lewin, Richard J. Young, Annie Wong, Robert Fuller, John Spillane, David Speakman, Simon Donahoe, Miklos Pohl, David Gyorki, Michael A. Henderson, Ricky W. Johnstone, Anthony T. Papenfuss, Mark Shackleton

Clinico-pathological characteristics of patients who donated melanomas.


Peter MacCallum Cancer Centre, the Australian National Health and Medical Research Council, the Victorian Cancer Agency, and Melbourne Melanoma Project

the Australian National Health and Medical Research Council, Pfizer Australia, and the Victorian Endowment for Science, Knowledge and Innovation

Cancer Council of Victoria

Victorian Cancer Agency and the Australian National Health and Medical Research Council

Australian National Health and Medical Research Council



The stability of markers that identify cancer cells that propagate disease is important to the outcomes of targeted therapy strategies. In human melanoma, conflicting data exist as to whether hierarchical expression of CD271/p75/NGFR (nerve growth factor receptor) marks cells with enriched tumorigenicity, which would compel their specific targeting in therapy. To test whether these discrepancies relate to differences among groups in assay approaches, we undertook side-by-side testing of published methods of patient-derived melanoma xenografting (PDX), including comparisons of tissue digestion procedures or coinjected Matrigel formulations. We found that CD271− and CD271+ melanoma cells from each of seven patients were similarly tumorigenic, regardless of assay variations. Surprisingly variable CD271 expression patterns were observed in the analyses of sibling PDX tumors (n = 68) grown in the same experiments from either CD271− or CD271+ cells obtained from patients. This indicates unstable intratumoral lineage relationships between CD271− and CD271+ melanoma cells that are inconsistent with classical, epigenetically based theories of disease progression, such as the cancer stem cell and plasticity models. SNP genotyping of pairs of sibling PDX tumors grown from phenotypically identical CD271− or CD271+ cells showed large pairwise differences in copy number (28%–48%). Differences were also apparent in the copy number profiles of CD271− and CD271+ cells purified directly from each of the four melanomas (1.4%–23%). Thus, CD271 expression in patient melanomas is unstable, not consistently linked to increased tumorigenicity and associated with genetic heterogeneity, undermining its use as a marker in clinical studies. Cancer Res; 76(13); 3965–77. ©2016 AACR.