Multiplatform Analysis of Intratumoral PTEN Heterogeneity in Melanoma.

Abstract

Loss of protein expression of the tumor suppressor PTEN is associated with increased cancer aggressiveness, decreased tumor immune infiltration, and resistance to immune and targeted therapies in melanoma. We assessed a unique cohort of eight melanoma samples with focal loss of PTEN protein expression to understand the features and mechanisms of PTEN loss in this disease. We compared the PTEN-negative (PTEN[-]) areas to their adjacent PTEN-positive (PTEN[+]) areas using DNA sequencing, DNA methylation, RNA expression, digital spatial profiling, and immunohistochemical platforms. Variations or homozygous deletions of PTEN were identified in PTEN(-) areas that were not detected in the adjacent PTEN(+) areas in three cases (37.5%), but no clear genomic or DNA methylation basis for loss was identified in the remaining PTEN(-) samples. RNA expression data from two independent platforms identified a consistent increase in chromosome segregation gene expression in PTEN(-) versus adjacent PTEN(+) areas. Proteomic analysis showed a relative paucity of tumor-infiltrating lymphocytes in PTEN(-) versus adjacent PTEN(+) areas. The findings add to our understanding of potential molecular intratumoral heterogeneity in melanoma and the features associated with the loss of PTEN protein in this disease.

• Authors: Sharmeen Chagani, Mariana P De Macedo, Fernando Carapeto, Feng Wang, Diego M Marzese, Khalida Wani, Lauren E Haydu, Weiyi Peng, Giang T Ong, Sarah E Warren, Joseph M Beechem, Dave S B Hoon, Gordon B Mills, Michael T Tetzlaff, Alexander J Lazar, Lawrence N Kwong, Michael A Davies
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 143 Issue 9 Pg. 1779-1787.e1 (09 2023) ISSN: 1523-1747 [Electronic] United States
• PMID: 36871660 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• PTEN Phosphohydrolase
• RNA
• PTEN protein, human

Topics

• Humans
• PTEN Phosphohydrolase (genetics)
• Proteomics
• Melanoma (genetics, pathology)
• Genes, Tumor Suppressor
• RNA