Melanoma: identification of a gene essential for tumor growth
Melanoma is a cancer characterized by increased danger due to its rapid growth and propensity to metastasize. In an article published in the journal Cell Reports, Dr. Coin and Dr. Davidson's teams identify a gene crucial to tumor implantation, growth and dissemination: BAHCC1. By inhibiting this gene, they show a reduction in cell proliferation and a delay in DNA repair mechanisms, highlighting a new therapeutic target.
Cutaneous melanoma remains the most lethal skin cancer, even though its incidence has continued to rise in recent decades. Despite the significant improvement in five-year overall survival achieved by targeted therapies or immunotherapy, many patients eventually develop resistance, partly due to the plasticity of melanoma cells. This plasticity is due to adaptation to microenvironmental changes and drug exposure. It gives rise to significant intra-tumoral heterogeneity involving multiple cellular states.
Uveal melanoma is a form of melanoma involving a primary intraocular tumor, and is most common in adults. A high percentage of these patients develop metastases that are highly refractory to existing treatments. A better understanding of the molecular mechanisms involved in these two types of cancer could lead to the development of effective treatments.
In order to find new genes specifically expressed in these two types of melanoma, the researchers characterized the epigenetic landscape of several patient-derived cutaneous or uveal melanoma cultures. Integrative epigenomic analyses revealed the specific expression in a wide range of these cells of a gene encoding the Bromo Adjacent Homology and Coiled Coil Domain-Containing 1 (BAHCC1) protein. BAHCC1 promotes the proliferation of cutaneous and uveal melanoma cells, and is required for in vivo implantation and tumor growth. Loss-of-function and genomic profiling experiments show that BAHCC1 is a transcriptional regulator controlling the expression of a set of genes involved in cell cycle and DNA repair. Consistent with this putative role, depletion of BAHCC1 delays DNA repair in these cells and induces their death following exposure to DNA-damaging agents.
The researchers have thus identified a gene specifically expressed in melanoma cells, and demonstrate how its inhibition can be exploited to impede cell proliferation, either alone or in conjunction with DNA damage-inducing agents.