Pancreatic cancer is a highly heterogeneous disease that often has a poor prognosis. Development of drugs or treatment strategies to target cancers, including pancreatic cancer, depends on identifying the drivers of disease. These are the genes that promote carcinogenesis and coordinate development of the cancer. But by the time a patient is diagnosed, it can often be very difficult to tell which of the many mutations present in the tumor are actually disease drivers, and which are just along for the ride. Read more
One of the many remarkable findings of the cancer genome sequencing projects that have been published in this and other journals is the repeated discovery of somatic driver mutations in genes that encode chromatin remodeling factors, which regulate the epigenome. De novo mutations in this same family of genes also cause several developmental syndromes, whose various features all include intellectual disability. Surprisingly, a few de novo mutations in these genes have recently been reported in autism. How do these mutations (which at least in some cases appear to be loss-of-function in both cancer and in the developmental syndromes) in the same class, and in some cases, the same exact genes cause these different diseases? Read more
Glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG) are aggressive subtypes of brain tumors that both have a very poor prognosis and are almost always lethal. Two new studies in Nature and this journal today identify the same recurrent mutations in H3F3A in pediatric cases of glioblastoma multiforme and diffuse intrinsic pontine glioma. These are the first reports of human disease associated with mutations in histones, which play an extraordinarily important and conserved role in chromatin structure and gene regulation. With the recent spate of papers reporting somatic mutations in chromatin remodelers in various types of cancer (examples from this journal alone include the histone H3K27 demethylase UTX, transitional cell carcinoma of the bladder, histone methyltransferase EZH2 in follicular and diffuse large B-cell lymphoma and myeloid disorders, DNMT3A in AML, ARID2 in hepatocellular carcinoma, MLL2 in DLBCL, and ARID1a in gastric cancer) it is clear that targeting the chromatin remodeling machinery will be an important area in the development of new cancer drugs. Read more
