{"entity":{"id":"paper-nik-zainal-life-history-21-breast-cancers-cell-2012","kind":"paper","name":"The life history of 21 breast cancers","aka":[],"tldr":"By reading 21 breast cancer genomes deeply, researchers showed that most of a tumour's mutations are carried by only some of its cells, and that every tumour had a dominant branch.","summary":"The abstract reports that subclonal diversification is prominent, that most mutations are found in just a fraction of tumour cells, and that every tumour has a dominant subclonal lineage representing more than 50 per cent of tumour cells. The full text states that subclonal point mutations were found in all samples studied and that their estimated number genome-wide was, for most samples, more than the number of fully clonal mutations. One ER-positive tumour with a distinctive mutator pattern was sequenced to 188-fold depth to find low-fraction mutations: 70,690 somatic substitutions, many supported by fewer than 5 per cent of reads, including a cluster of about 15,600 found in about 65 per cent of tumour cells.","asOf":"2026-11-04","links":[{"label":"Nik-Zainal et al., Cell 2012","url":"https://doi.org/10.1016/j.cell.2012.04.023"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22608083/"}],"tags":[],"related":[],"cancers":["breast-cancer"],"sections":["diagnostics"],"technologies":["wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-subclone-attribution-residual-disease","b-tumor-heterogeneity"],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2012,"doi":"10.1016/j.cell.2012.04.023","pmid":"22608083","authors":"Nik-Zainal S, Van Loo P, Wedge DC, et al.","paperType":"translational","findings":["Most mutations are found in just a fraction of tumour cells.","Subclonal point mutations in every sample; for most, more subclonal than fully clonal (full text).","Finding low-fraction mutations needed deep sequencing (188-fold in the showcase tumour, which had an unusual mutator pattern)."],"whatItMeans":"Breast cancers are not short of subclonal mutations; they are hard to find without deep sequencing of the tumour, and residual disease panels that keep only high-fraction mutations leave them out.","caveats":["21 tumours.","The 188-fold case was chosen for an unusual mutator pattern and is not typical in its mutation count."],"participants":21},"route":"/key-papers/paper-nik-zainal-life-history-21-breast-cancers-cell-2012/","neighbours":{"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"technology":[{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"bottleneck":[{"id":"b-subclone-attribution-residual-disease","kind":"bottleneck","name":"Naming which clone or phenotype is left after treatment","route":"/bottlenecks/b-subclone-attribution-residual-disease/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}],"journal":[{"id":"cell","kind":"journal","name":"Cell","route":"/journals/cell/"}]}}