Subklonale

Subklonale, often translated as subclonal, refers to genetic or phenotypic variants that exist only in a subset of cells within a larger clonal population. The term is widely used in cancer genomics to describe intratumoral heterogeneity arising from clonal evolution. Subklonal populations emerge after an initial oncogenic event, through accumulating somatic mutations, copy-number alterations, or epigenetic changes, and may coexist with the ancestral clone.

Detection and characterization rely on sequencing data. In bulk tumor sequencing, subclonal mutations exhibit a reduced cancer cell fraction compared with clonal mutations, allowing computational methods to infer the number and composition of subclones. Tools such as PyClone, SciClone or ABSOLUTE estimate clonal architecture, while single-cell sequencing can resolve subclones directly, albeit at higher cost and complexity. Spatially resolved or multi-region sequencing reveals how subclones are distributed within a tumor, and longitudinal sampling can track clonal dynamics under therapy.

The presence of subclones has major implications for disease progression and treatment. Subclonal driver mutations can seed metastases or drive resistance to targeted therapies; therapeutic pressure often selects for resistant subclones, leading to relapse. This has spurred interest in monitoring tumor evolution through liquid biopsy and in designing combination strategies that target multiple clonal and subclonal populations.

Challenges include distinguishing true subclonal variants from sequencing or copy-number artefacts, accounting for tumor purity, and addressing sampling bias. Despite advances, subklonal analysis remains an active area in cancer genomics, with ongoing research aiming to map clonal architectures more accurately and use them to guide therapy.