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Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs’ recapitulation of human tumors., Patient-derived xenograft models (PDX) have been extensively used to study the molecular and clinical features of cancers. Here the authors present a cohort of 536 PDX models from 25 cancers, as well as their genomic and evolutionary profiles and their suitability for clinical trials.

Increased solar radiation and other unknown factors induce excess melanin production in melanocytes accumulated in localized areas of the skin, leading to formation of benign nevi and infrequently, dysplastic nevi that may progress to melanoma. I hypothesized that excess melanin production in melanocytes of such nevi may cause physico-chemical constraints on the metabolic activities of DNA and RNA, which, in rare instances, may induce pro-survival responses, including oncogenic mutations, in cellular DNA. This may lead to selective transcription and/or translation that support oncogenic transformation of one or more of these cells. To test this hypothesis, long-term production of excess melanin in melanocytes derived from fair-skinned and dark-skinned individuals was induced with chronic tyrosine exposure or chronic UV-radiation treatment. Long-term melanin production in cells from fair-skinned individuals caused a small increase in their proliferation. Chronic melanin production over a period of six months revealed unique gene expression patterns associated with growth promoting signaling networks in melanocytes from fair-skinned individuals. Functional cell biological analyses revealed that these effects resulted in increased proliferation and transformative potential of the melanocytes derived from fair-skinned, but not dark-skinned individuals. This study suggests that melanin pigment may play an important role in the oncogenic transformation of melanocytes from fair-skinned individuals.