Subclonal

Subclonal refers to a population of cells within a larger clone that carries distinct genetic or epigenetic alterations not shared by all members of the original clone. In cancer biology, a tumor is often composed of a dominant clone and one or more subclonal lineages that arise through successive mutations, chromosomal rearrangements, or epigenetic changes. These subclones coexist within the same tissue, competing for resources and influencing disease progression.

The presence of subclonal diversity is a hallmark of intratumoral heterogeneity. It can drive treatment resistance, as therapies targeting mutations present in the dominant clone may spare subclones that lack those alterations, allowing them to expand under selective pressure. Conversely, subclonal mutations may provide biomarkers for early detection of relapse or for tailoring combination therapies.

Subclonal architecture is typically reconstructed using high‑throughput sequencing data. Methods such as deep targeted sequencing, whole‑exome or whole‑genome sequencing, and single‑cell genomics are employed to estimate variant allele frequencies, infer phylogenetic relationships, and quantify the proportion of each subclone. Computational tools like PyClone, SciClone, and PhyloWGS model the clonal hierarchy and estimate cancer cell fractions.

Beyond oncology, the term is used in immunology to describe B‑cell or T‑cell populations derived from a common ancestor but diversified by somatic hypermutation or antigen-driven selection. In evolutionary biology, subclonal lineages can illustrate microevolutionary processes within microbial communities or plant populations. Understanding subclonal dynamics enhances insights into disease evolution, therapeutic response, and the broader mechanisms of biological diversification.