Copy-number intratumor heterogeneity as high-risk feature of stage II colon cancer^†

Overall, the prognosis of patients suffering from stage II colon cancer is relatively favorable. However, a proportion of patients develop a recurrence following surgery. Clinical and histopathological properties that identify high-risk patients are of limited value and better biomarkers are urgently required. In a recent issue of The Journal of Pathology, Lahoz et al proposed that copy-number-based biomarkers could be employed for patient stratification. The authors studied copy-number alterations (CNAs) at the genomic scale by measuring the total CNA load (the aberrant genome fraction), and at a smaller scale by identifying common arm- or cytoband-level alterations. Both the overall CNA load and specific chromosomal regions were associated with an increased risk of recurrence. Most interestingly, it was demonstrated that copy-number intratumor heterogeneity, as defined by subclonal CNAs, is associated with poor disease outcome. This study demonstrates that structural genomic aberrations are promising biomarkers for patient stratification in early colon cancer. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.