Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone

It is recognized that some mutated cancer genes contribute to the development of many cancer types, whereas others are cancer type specific. For genes that are mutated in multiple cancer classes, mutations are usually similar in the different affected cancer types. Here, however, we report exquisite tumor type specificity for different histone H3.3 driver alterations. In 73 of 77 cases of chondroblastoma (95%), we found p.Lys36Met alterations predominantly encoded in H3F3B, which is one of two genes for histone H3.3. In contrast, in 92% (49/53) of giant cell tumors of bone, we found histone H3.3 alterations exclusively in H3F3A, leading to p.Gly34Trp or, in one case, p.Gly34Leu alterations. The mutations were restricted to the stromal cell population and were not detected in osteoclasts or their precursors. In the context of previously reported H3F3A mutations encoding p.Lys27Met and p.Gly34Arg or p.Gly34Val alterations in childhood brain tumors, a remarkable picture of tumor type specificity for histone H3.3 driver alterations emerges, indicating that histone H3.3 residues, mutations and genes have distinct functions.

Neoliberalism in Britain

The Conservative Party has in the 2015 British general elections won an absolute majority under David Cameron’s leadership. Cameron’s rule signifies an important phase in British politics in the 21st century. This paper asks the question: What is Cameronism? Cameron argues that Margaret Thatcher “was a big influence” for him. It is therefore appropriate to study the relationship between Thatcherism and Cameronism. The article revisits theories of Thatcherism and understands it as a unity of ideology and policies that is organised along three dimensions: the economy, politics, and culture. An ideology critique study of key speeches, interviews and documents analyses these three dimensions of Cameronism. A comparison of Cameronism and Thatcherism shows that questions of national identity, the European Union and immigration form a key ideological and political dimension of Cameronism.