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Published on: September 15, 2023
Molecular changes in the phosphatidylinositide 3-kinase (PI3K) pathway are common in gastric cancer
Thang N Tran1, Kate Brettingham-Moore, Cuong P Duong
1Surgical Oncology Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Background And Objectives:
The phosphatidylinositide 3-kinase (PI3K) pathway is an important signalling pathway that is frequently activated in cancer cells. This has led to the emergence of PI3K inhibitors as potential new treatment modalities for many cancers. We have investigated the frequency of molecular changes in the PI3K pathway in gastric cancer.
Methods:
A series of sixty one human gastric cancer specimens and nine human gastric cancer cell lines were screened for PIK3CA mutations and copy number gain by direct sequencing and multiplex ligation-dependent probe amplification (MLPA), respectively. PTEN protein levels were assessed by immunohistochemistry.
Results:
Alterations in the PI3K pathway were found in 33 of 61 (54%) gastric tumours. PIK3CA mutation and copy number gain were detected in 3 (4.9%) and 8 (13.1%), respectively, of 61 gastric cancer samples while PTEN loss was detected in 24 (39%) of the tumours. Two tumours had both PTEN loss and PIK3CA copy number gain. There were no significant associations between these PI3K pathway changes and the clinical features of the tumours.
Conclusions:
Alterations in the PI3K pathway are frequent in gastric tumours implicating this pathway as a legitimate therapeutic target in gastric cancer.
Insights
Molecular alterations in the phosphatidylinositide 3-kinase (PI3K) pathway are common in gastric cancer. These frequent PI3K pathway changes suggest it is a viable therapeutic target for treating this disease.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- The phosphatidylinositide 3-kinase (PI3K) pathway is crucial in cellular signaling and frequently dysregulated in various cancers.
- PI3K inhibitors are emerging as promising therapeutic agents for cancer treatment.
- Understanding PI3K pathway alterations in gastric cancer is essential for targeted therapy development.
Purpose of the Study:
- To determine the frequency of molecular alterations within the PI3K pathway in human gastric cancer specimens and cell lines.
- To investigate the prevalence of PIK3CA mutations, copy number gains, and PTEN loss in gastric tumors.
- To explore potential associations between PI3K pathway alterations and clinical features of gastric cancer.
Main Methods:
- Screening of 61 gastric cancer specimens and 9 cell lines for PIK3CA mutations using direct sequencing.
- Assessment of PIK3CA copy number gain via multiplex ligation-dependent probe amplification (MLPA).
- Evaluation of PTEN protein levels using immunohistochemistry.
Main Results:
- PI3K pathway alterations were identified in 54% (33/61) of gastric tumors.
- PIK3CA mutations occurred in 4.9% (3/61) and copy number gains in 13.1% (8/61) of samples.
- PTEN loss was observed in 39% (24/61) of tumors; no significant associations with clinical features were found.
Conclusions:
- Frequent alterations in the PI3K pathway underscore its significance in gastric tumorigenesis.
- The PI3K pathway represents a rational and validated therapeutic target for gastric cancer treatment.
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