Related Experiment Video
Updated: Aug 8, 2025
Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
Multiplatform Analysis of Intratumoral PTEN Heterogeneity in Melanoma
Sharmeen Chagani1, Mariana P De Macedo1, Fernando Carapeto1
1Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
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.
Insights
Loss of phosphatase and tensin homolog (PTEN) protein in melanoma is linked to aggressive tumors and reduced immune cell infiltration. This study explored PTEN loss mechanisms, revealing increased chromosome segregation gene expression in PTEN-negative areas.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Loss of phosphatase and tensin homolog (PTEN) protein expression correlates with increased melanoma aggressiveness.
- PTEN loss is associated with decreased tumor immune infiltration and resistance to therapies.
- Understanding PTEN loss mechanisms is crucial for melanoma treatment strategies.
Purpose of the Study:
- To investigate the molecular features and mechanisms underlying focal loss of PTEN protein expression in melanoma.
- To compare PTEN-negative (PTEN[-]) areas with adjacent PTEN-positive (PTEN[+]) areas within melanoma samples.
- To elucidate the role of PTEN loss in melanoma intratumoral heterogeneity.
Main Methods:
- Analysis of a cohort of eight melanoma samples with focal PTEN protein loss.
- Utilized DNA sequencing, DNA methylation, RNA expression, digital spatial profiling, and immunohistochemistry.
- Compared PTEN(-) and PTEN(+) regions within individual samples.
Main Results:
- Genetic variations or homozygous deletions in PTEN were found in PTEN(-) areas in 37.5% of cases.
- No clear genomic or DNA methylation basis for PTEN loss was identified in the remaining samples.
- Increased expression of chromosome segregation genes and decreased tumor-infiltrating lymphocytes were observed in PTEN(-) areas.
Conclusions:
- PTEN loss in melanoma can occur through genetic alterations or other unidentified mechanisms.
- PTEN-negative melanoma regions exhibit distinct molecular features, including altered gene expression and immune microenvironment.
- Findings highlight PTEN loss as a contributor to molecular intratumoral heterogeneity in melanoma.
