Dataset Information

G9a: An Emerging Epigenetic Target for Melanoma Therapy.

ABSTRACT: Epigenetic regulation is a crucial component of DNA maintenance and cellular identity. As our understanding of the vast array of proteins that contribute to chromatin accessibility has advanced, the role of epigenetic remodelers in disease has become more apparent. G9a is a histone methyltransferase that contributes to immune cell differentiation and function, neuronal development, and has been implicated in diseases, including cancer. In melanoma, recurrent mutations and amplifications of G9a have led to its identification as a therapeutic target. The pathways that are regulated by G9a provide an insight into relevant biomarkers for patient stratification. Future work is aided by the breadth of literature on G9a function during normal differentiation and development, along with similarities to EZH2, another histone methyltransferase that forms a synthetic lethal relationship with members of the SWI/SNF complex in certain cancers. Here, we review the literature on G9a, its role in melanoma, and lessons from EZH2 inhibitor studies.

SUBMITTER: Flesher JL

PROVIDER: S-EPMC8536146 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

G9a: An Emerging Epigenetic Target for Melanoma Therapy.

Flesher Jessica L JL Fisher David E DE

Epigenomes 20211012 4

Epigenetic regulation is a crucial component of DNA maintenance and cellular identity. As our understanding of the vast array of proteins that contribute to chromatin accessibility has advanced, the role of epigenetic remodelers in disease has become more apparent. G9a is a histone methyltransferase that contributes to immune cell differentiation and function, neuronal development, and has been implicated in diseases, including cancer. In melanoma, recurrent mutations and amplifications of G9a h ...[more]

PMID: 34691767

Similar Datasets

Project description:Recent sequencing efforts in melanoma have elucidated many previously unknown molecular pathways and biological mechanisms involved in melanoma development and progression and have yielded a number of promising targets for molecular therapy. As sequencing technologies have become more sophisticated and have revealed an ever-increasing complexity of the genetic landscape of melanoma, it has become clear that sequencing methods applied to clinical specimens have to reliably capture not only recurrent "hotspot" mutations like BRAFV600 and NRASQ61 or "mini-hotspot" mutations like exon 11 and 13 c-KIT but also heterogeneous somatic mutations dispersed across multiple functionally conserved regions of genes or entire genes. One such example in melanoma is the ERBB4 receptor, or HER4, a member of the Erb receptor family, which has recently been shown to be a major oncogenic "driver" in melanoma. Mutated ERBB4 signaling activates both aberrant ERBB4 and PI3K-AKT signal transduction, mediates sensitivity to small-molecule inhibition with the dual-tyrosine kinase inhibitor lapatinib, and has recently also been implied in oncogenic glutamatergic signaling in melanoma. Mutations involving the ERBB4 gene act as "gain-of-function" mutations and predominantly involve the extracellular domains of the receptor. Additional sequencing efforts have recently identified recurrent mutations ("mini-hotspots") or mutation clusters which affect the regulation of, e.g., ligand binding, arrangement of extracellular domain alignment, or intramolecular tether formation.In this chapter, we describe the methods used to determine the mutation status of all exons of the ERBB4 gene in clinical specimens obtained from patients afflicted by metastatic melanoma. Upon slight modifications, this protocol can also be used for mutational analysis of other oncogenes affected by "non-hotspot" mutations dispersed across multiple exons. This sequencing technique has successfully been applied within a clinical trial selecting patients with ERBB4-mutant melanoma for lapatinib treatment. With the increasing emergence of low-frequency oncogenes affected by heterogeneous activating mutations located in different exons and regions this method will provide a mean to translate the promise of recently obtained genetic knowledge into clinical genotype-directed targeted therapy trials.

Dataset Information

G9a: An Emerging Epigenetic Target for Melanoma Therapy.

Publications

G9a: An Emerging Epigenetic Target for Melanoma Therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets