Elsevier

Cancer Genetics

Volume 208, Issue 5, May 2015, Pages 178-191
Cancer Genetics

Contributions to Progress and Promise of Epigenetics for Diagnosis and Therapy in Cancer
The cancer COMPASS: navigating the functions of MLL complexes in cancer

https://doi.org/10.1016/j.cancergen.2015.01.005Get rights and content

The mixed-lineage leukemia family of histone methyltransferases (MLL1–4, or KMT2A–D) were previously linked to cancer through the founding member, MLL1/KMT2A, which is often involved in translocation-associated gene fusion events in childhood leukemias. However, in recent years, a multitude of tumor exome sequencing studies have revealed that orthologues MLL3/KMT2C and MLL2/KMT2D are mutated in a significant percentage of a large variety of malignancies, particularly solid tumors. These unexpected findings necessitate a deeper inspection into the activities and functional differences between the MLL/KMT2 family members. This review provides an overview of this protein family and its relation to cancers, focusing on the recent links between MLL3/KMT2C and MLL2/4/KMT2D and their potential roles as tumor suppressors in an assortment of cell types.

Section snippets

Chromatin and epigenetic modifiers in cancer

During the processes of organismal development and cellular differentiation, somatic cells receive both internal and external cues that lead to the reprogramming of the genome with consequent coordinated changes in gene expression. When these signals are imposed on stem cells, the cells respond through a series of developmental steps to become progenitor cells that will continue on a path of lineage commitment and become fully differentiated. Disruptions of these pathways can lead to a block in

Conclusions and perspectives

Since the discovery of MLL1/KMT2A translocations in acute leukemia in 1991, we have acquired valuable insights into the important roles that histone modifications play in controlling the expression of genes found to be dysregulated in cancer, and into epigenetics in general. Within the past several years, the availability of fully sequenced genomes, exomes, epigenomes, and transcriptomes has allowed us a greatly expanded view of the range of gene mutations associated with many cancers. The

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