Melanoma-patient-derived xenograft multi-omics resource melPDomiX maps gain- and loss-of-function alterations

Konstantinos Tsingas1, Monzy Thomas2, McKenna Reale2

  • 1Molecular and Cellular Oncogenesis Program, Melanoma Research Center, The Wistar Institute, Philadelphia, Philadelphia, PA 19104, USA; University of Pennsylvania, Philadelphia, PA 19104, USA.

Cell Reports
|June 3, 2026
PubMed

Insights

Researchers created melPDomiX, a multi-omics resource of melanoma patient-derived xenografts. This helps understand gene changes in refractory melanoma, identifying new drivers and therapeutic targets for improved cancer treatments.

Area of Science:

  • Oncology
  • Genomics
  • Proteomics

Background:

  • Melanoma is an aggressive cancer with increasing incidence.
  • Current treatments are ineffective for some patients due to incomplete understanding of melanoma tumorigenesis.
  • There is a need for comprehensive resources to study gene and pathway alterations in refractory melanoma.

Purpose of the Study:

  • To establish melPDomiX, a multi-omics cohort of melanoma patient-derived xenografts.
  • To systematically characterize gain- and loss-of-function alterations in treatment-refractory melanoma.
  • To identify novel melanoma drivers and therapeutic targets.

Main Methods:

  • Established a multi-omics cohort of melanoma patient-derived xenografts (melPDomiX).
  • Linked mutations with transcriptomic and proteomic features.
  • Utilized multi-omics integration and structural-context representation to distinguish variant functions.

Main Results:

  • melPDomiX enables systematic characterization of genetic alterations in refractory melanoma.
  • The resource successfully distinguishes gain- from loss-of-function variants.
  • New candidate melanoma drivers and therapeutic targets were uncovered.

Conclusions:

  • melPDomiX is a valuable resource for mechanistic discovery in melanoma.
  • This multi-omics approach facilitates the development of improved treatments for heterogeneous melanoma.
  • Understanding gene and pathway alterations is crucial for overcoming treatment resistance.

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