PI3KCA Mutations in Uterine Cervix Carcinoma
1Algoma District Cancer Program, Sault Area Hospital, Sault Ste. Marie, ON P6B 0A8, Canada.
Background:
Squamous cervical carcinoma represents an infection-associated malignancy that produces a high mortality when metastatic or recurrent after primary local treatment. There is an urgent need for new therapies for this cancer. Molecular lesions in cervical cancer may provide opportunities for targeted therapies development.
Methods:
Publicly available data from the Cancer Genome Atlas (TCGA) were analyzed to define the molecular landscape of squamous cervical carcinomas with and without mutations of PIK3CA, the gene encoding the alpha catalytic subunit of phosphatidylinositol 3 kinase (PI3K). Associations with alterations in other critical genes and pathways of cancer and the total mutation burden and copy number alteration burden of cervical cancers were examined.
Results:
Mutations in PIK3CA are observed in 27.1% of squamous cervical cancers. PIK3CA represents the most frequently mutated gene in these cancers. Mutations in PIK3CA are associated with higher rates of mutations in other genes of important cancer-associated pathways such as the tyrosine kinase receptors/K-Ras/BRAF/MAPK and the Wnt/β catenin pathway. In addition, PIK3CA mutated cervical cancers display a higher tumor mutation burden (TMB) than non-mutated cancers.
Conclusion:
Frequent mutations of PIK3CA gene in squamous cervical carcinomas may represent an opportunity for targeted therapies development both inhibiting the PI3K kinase and associated pathway defects. Increased TMB may additionally confer immunotherapy sensitivity.
Insights
Frequent PIK3CA gene mutations in squamous cervical cancer offer targeted therapy opportunities. These PIK3CA-mutated cancers also show higher tumor mutation burden, potentially improving immunotherapy response.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Squamous cervical carcinoma is an infection-associated malignancy with high mortality, especially when metastatic or recurrent.
- Existing treatments for cervical cancer are insufficient, highlighting the need for novel therapeutic strategies.
- Identifying molecular alterations in cervical cancer is crucial for developing targeted therapies.
Purpose of the Study:
- To define the molecular landscape of squamous cervical carcinomas.
- To investigate the role of PIK3CA gene mutations in cervical cancer.
- To explore associations between PIK3CA mutations and other cancer-related genetic alterations and tumor mutational burden.
Main Methods:
- Analysis of publicly available data from The Cancer Genome Atlas (TCGA).
- Examination of squamous cervical carcinomas with and without PIK3CA mutations.
- Assessment of associations with alterations in critical cancer genes/pathways and tumor mutational burden.
Main Results:
- PIK3CA mutations were found in 27.1% of squamous cervical cancers, making it the most frequently mutated gene.
- PIK3CA mutations correlated with increased mutations in key cancer pathways, including tyrosine kinase receptors/MAPK and Wnt/β catenin.
- Cervical cancers with PIK3CA mutations exhibited a significantly higher tumor mutation burden (TMB) compared to non-mutated cancers.
Conclusions:
- Frequent PIK3CA gene mutations in squamous cervical cancer present a therapeutic target for PI3K inhibitors and associated pathway modulators.
- Elevated TMB in PIK3CA-mutated tumors suggests potential sensitivity to immunotherapy.
- Targeting PIK3CA and related pathways holds promise for improved cervical cancer treatment outcomes.
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