Genetics and Prognostication in Splenic Marginal Zone Lymphoma: Revelations from Deep Sequencing

Purpose: Mounting evidence supports the clinical significance of gene mutations and immunogenetic features in common mature B-cell malignancies.

Experimental Design: We undertook a detailed characterization of the genetic background of splenic marginal zone lymphoma (SMZL), using targeted resequencing and explored potential clinical implications in a multinational cohort of 175 patients with SMZL.

Results: We identified recurrent mutations in TP53 (16%), KLF2 (12%), NOTCH2 (10%), TNFAIP3 (7%), MLL2 (11%), MYD88 (7%), and ARID1A (6%), all genes known to be targeted by somatic mutation in SMZL. KLF2 mutations were early, clonal events, enriched in patients with del(7q) and IGHV1-2*04 B-cell receptor immunoglobulins, and were associated with a short median time to first treatment (0.12 vs. 1.11 years; P = 0.01). In multivariate analysis, mutations in NOTCH2 [HR, 2.12; 95% confidence interval (CI), 1.02–4.4; P = 0.044] and 100% germline IGHV gene identity (HR, 2.19; 95% CI, 1.05–4.55; P = 0.036) were independent markers of short time to first treatment, whereas TP53 mutations were an independent marker of short overall survival (HR, 2.36; 95 % CI, 1.08–5.2; P = 0.03).

Conclusions: We identify key associations between gene mutations and clinical outcome, demonstrating for the first time that NOTCH2 and TP53 gene mutations are independent markers of reduced treatment-free and overall survival, respectively.

’Letting the right one in’: provider contexts for recruitment to initial teacher education in the United Kingdom

We exploit policy differences within the UK to investigate provider context and recruitment to initial teacher education (ITE). We identify three dimensions of variation: conceptions of professionalism, universal or context specific preparation and costs and benefits to providers. University-led ITE programmes used similar criteria and processes in each jurisdiction, but there were differences between university-led and school-led recruitment. Our study suggests that the current shortfall in recruitment to ITE in England may be a product of the contextual constraints which schools experience. It also suggests that school-led recruitment may tend to emphasise short-term and school-specific needs.

Three dimensional Sklyanin algebras and Gröbner bases

We consider Sklyanin algebras $S$ with 3 generators, which are quadratic algebras over a field $\K$ with $3$ generators $x,y,z$ given by $3$ relations $pxy+qyx+rzz=0$, $pyz+qzy+rxx=0$ and $pzx+qxz+ryy=0$, where $p,q,r\in\K$. this class of algebras has enjoyed much attention. In particular, using tools from algebraic geometry, Feigin, Odesskii \cite{odf}, and Artin, Tate and Van Den Bergh, showed that if at least two of the parameters $p$, $q$ and $r$ are non-zero and at least two of three numbers $p^3$, $q^3$ and $r^3$ are distinct, then $S$ is Artin--Schelter regular. More specifically, $S$ is Koszul and has the same Hilbert series as the algebra of commutative polynomials in 3 indeterminates (PHS). It has became commonly accepted that it is impossible to achieve the same objective by purely algebraic and combinatorial means like the Groebner basis technique. The main purpose of this paper is to trace the combinatorial meaning of the properties of Sklyanin algebras, such as Koszulity, PBW, PHS, Calabi-Yau, and to give a new constructive proof of the above facts due to Artin, Tate and Van Den Bergh. Further, we study a wider class of Sklyanin algebras, namely
the situation when all parameters of relations could be different. We call them generalized Sklyanin algebras. We classify up to isomorphism all generalized Sklyanin algebras with the same Hilbert series as commutative polynomials on
3 variables. We show that generalized Sklyanin algebras in general position have a Golod–Shafarevich Hilbert series (with exception of the case of field with two elements).