At least two well-spaced samples are needed to genotype a solid tumor.

Area of Science:

• Oncology
• Genomics
• Cancer Research

Background:

• Human cancers exhibit spatial heterogeneity with public and private mutations.
• Understanding mutation distribution is key to accurate tumor sampling.
• Single tumor samples may not capture full heterogeneity.

Purpose of the Study:

• To evaluate the efficacy of single versus multiple tumor samples in classifying mutations.
• To determine if two samples improve the identification of public and private mutations in colorectal cancer.

Main Methods:

• Analysis of 12 human colorectal tumors with known mutations.
• Comparison of mutation classification accuracy using one versus two spatially-separated samples.
• Paired t-test used to assess statistical significance.

Main Results:

• Two samples significantly improved the identification of both public (99% vs. 97%) and private mutations (85% vs. 46%) compared to a single sample.
• Private mutations often appeared clonal in single samples, confounding accuracy.
• Two samples detected the most frequent private mutations in 11 out of 12 tumors.

Conclusions:

• Spatially-separated sampling efficiently distinguishes public from private mutations due to their heterogeneous distribution.
• The patchy nature of private mutations limits the information obtained from single tumor samples.
• Accurate identification of public and private mutations can inform targeted therapy strategies.