Abstract
The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in‐depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.
Highlights
Metastatic malignant melanoma carries a poor prognosis, surgical intervention of the primary melanoma is curative in most patients, which underlines the importance of early diagnosis
The present publication belongs to a series of two on the Human Melanoma Proteome published by Clinical and Translational Medicine
A significant set of melanoma samples showed low levels of tumor cells, which in most cases correlated to high stromal content
Summary
Metastatic malignant melanoma carries a poor prognosis, surgical intervention of the primary melanoma is curative in most patients, which underlines the importance of early diagnosis. In 2020, Globocan reported 324,635 new cases and 57,043 deaths (https://gco.iarc.fr)[1] from melanoma worldwide. In Sweden, melanoma ranks number 5-6 among cancers (incidence: 38/100,000 in 2019) and the 10-year survival approaches 90% as the proportion of thinner melanomas with an extremely good prognosis, increases.[5,6] Metastatic melanoma (MM) used to have an extremely poor prognosis until 10 years ago, since the development of modern drugs modulating the immune response or targeting specific cellular signaling events has prolonged survival from months to years for many patients.[7,8,9] some patients with MM do not fully respond or develop drug resistance to the novel treatments why there is still need for more mechanistic disease knowledge.[10,11,12] Clonal diversity and genetic inter- and intratumor heterogeneity in MM are in particular, poorly understood.[13,14,15,16]
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