Spatial mutation patterns as markers of early colorectal tumor cell mobility

Area of Science:

• Oncology
• Computational Biology
• Genetics

Background:

• Human cancers can arise from single clonal expansions, allowing for ancestral tree reconstruction.
• Understanding early tumor cell behavior is crucial for inferring tumor progression and metastatic potential.

Purpose of the Study:

• To investigate if early tumor cell mobility phenotypes can be inferred from ancestral tree reconstruction.
• To explore the link between early cell movement and private mutation patterns in colorectal tumors.

Main Methods:

• Development of a computational multiscale model of tumor expansion.
• Incorporation of glandular structure of colorectal tumors into the model.
• Calibration of the model using multiregional and single gland data from human colorectal tumors via approximate Bayesian computation.

Main Results:

• Simulations revealed that early cell mixing leads to variegated private mutation patterns, detectable on opposite tumor sides.
• Absence of early mixing resulted in non-variegated, sectional mutation patterns.
• Evidence of early abnormal cell movement was found in 9 of 15 invasive colorectal carcinomas, but not in benign adenomas.

Conclusions:

• Private mutation patterns in colorectal tumors may serve as markers for early cell movement and invasive potential.
• Early cell movement appears to be associated with invasive colorectal carcinomas.
• Further validation could establish private mutation patterns for outcome prediction in screen-detected lesions.