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A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells

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Double PIK3CA Alterations and Parallel Evolution in Colorectal Cancers.

Ming-Tseh Lin¹, Gang Zheng^1,2, Erika Rodriguez¹

¹Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

American Journal of Clinical Pathology

|September 14, 2021

Summary

Double PIK3CA alterations in colorectal cancer (CRC) are often clonal and arise from parallel evolution. Further research is needed to understand their clinical significance and guide targeted therapies.

Keywords:

Colorectal cancer Double PIK3CA Multiclonal CRC Parallel evolution mTOR pathway

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Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer

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Published on: July 28, 2010

Area of Science:

Oncology
Molecular Biology
Genetics

Background:

PIK3CA mutations are common in colorectal cancer (CRC).
The role of double PIK3CA alterations in CRC progression is not fully understood.

Purpose of the Study:

To investigate the clinicopathologic features of colorectal cancers (CRCs) with double PIK3CA alterations.
To evaluate the clonality and evolutionary patterns of these double alterations.

Main Methods:

Analysis of 13 CRCs with double PIK3CA alterations.
Multiregional tumor analyses to assess PIK3CA alteration clonality.
Examination of mutation status in common cancer-related genes (APC, KRAS).

Main Results:

Double PIK3CA alterations were found in 1.7% of CRCs, frequently involving exon 9 or 20.
Most double alterations were clonal, present within a single tumor population.
Multiregional analysis revealed multiclonal CRCs with divergent PIK3CA variants, originating from a common adenoma lineage.

Conclusions:

Findings support parallel evolution in CRC development, involving the MAPK or mTOR pathways.
Double PIK3CA alterations may arise through distinct evolutionary trajectories.
Further studies are crucial to determine the clinical significance and therapeutic potential for CRCs with double PIK3CA alterations.