Detecting truly clonal alterations from multi-region profiling of tumours

Area of Science:

• Oncology
• Genomics
• Cancer Biology

Background:

• Modern cancer therapies target specific tumor alterations for maximal efficacy.
• Accurate identification of tumor-wide alterations is crucial for treatment decisions.
• Current sampling methods may misclassify clonal versus sub-clonal alterations.

Purpose of the Study:

• To evaluate the impact of multi-region tumor sampling on identifying clonal alterations.
• To determine the optimal number of samples for accurate classification of tumor heterogeneity.
• To assess differences in tumor phylogenetics between colorectal and renal cell carcinoma.

Main Methods:

• Analysis of 181 samples from 10 renal cell carcinoma and 11 colorectal cancer patients.
• Phylogenetic analysis to classify clonal versus sub-clonal alterations.
• Evaluation of information gain from increased sampling density.

Main Results:

• In colorectal cancer, 30% of alterations identified as clonal with one biopsy were sub-clonal with eight samples.
• In renal cell carcinoma, eight samples reduced the clonal alteration list by 40% compared to a single biopsy.
• Overestimation of clonal alterations remained high (92%) in renal cell carcinoma even with eight samples.

Conclusions:

• Increased tumor sampling significantly refines the identification of clonal alterations.
• Renal cell carcinoma exhibits higher heterogeneity, requiring denser sampling than colorectal cancer.
• Tumor phylogenetic trees at relapse suggest a need for denser sampling to guide treatment.