AUTHOR=Henikoff Steven , Ahmad Kami 

TITLE=Hansemann’s anaplastic theory of cancer after 135 years

JOURNAL=Frontiers in Epigenetics and Epigenomics

VOLUME=Volume 3 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/epigenetics-and-epigenomics/articles/10.3389/freae.2025.1607433

DOI=10.3389/freae.2025.1607433

ISSN=2813-706X

ABSTRACT=Summary: The term “anaplasia” was coined in 1890 to describe chromosomal changes common to primordial cancer cells, but ever since the mechanisms whereby a cell becomes anaplastic has been the subject of much speculation. Recent results based on genomic and epigenomic profiles of cancer patient samples provide a glimpse into early events that lead to aneuploidy, the original defining feature of an anaplastic cell. We propose that the anaplastic cell is one in which RNA Polymerase II hypertranscribes S-phase-dependent histone genes, and the resulting histone excess facilitates DNA replication while competing for CENP-A, causing centromere breaks that initiate whole-arm aneuploidy.