Dissecting the pathogenesis of classical Hodgkin lymphoma (cHL), a common cancer in young adults, remains challenging because of the rarity of tumor cells in involved tissues (usually <5%). Here, we analyzed the coding genome of cHL by microdissecting tumor and normal cells from 34 patient biopsies for a total of ∼50 000 singly isolated lymphoma cells. We uncovered several recurrently mutated genes, namely, (32% of cases), (24%), (18%), and (16%), and document the functional role of mutant STAT6 in sustaining tumor cell viability. Mutations of genetically and functionally cooperated with disruption of, a JAK-STAT pathway inhibitor, to promote cHL growth. Overall, 87% of cases showed dysregulation of the JAK-STAT pathway by genetic alterations in multiple genes (also including ,, ,, and ), attesting to the pivotal role of this pathway in cHL pathogenesis and highlighting its potential as a new therapeutic target in this disease.

Our results suggest that MA and p53 mutations in tumor DNA have a potential prognostic role for disease recurrence in NSCLC patients, and elevated levels of plasma circulating DNA identify patients with possible systemic disease at diagnosis. This might be proposed as an early detection test of disease recurrence.

Biological effects of MNT delineate a complex picture of gene activation and repression, probably induced by Cys-LTR blockade. The induction of apoptosis in allergen-specific T cell population, as a final result, appears fundamental in the treatment of asthma.

BackgroundWe investigated whether GSTT1 (“null” allele), GSTM1 (“null”allele), GSTP1 (A313G), RFC1 (G80A), MTHFR (C677T), TS (2R/3R) polymorphisms were associated with toxicity and survival in patients with early breast cancer (EBC) treated with adjuvant chemotherapy (CT).MethodsThis prospective trial included patients with stage I–III BC subjected to CT with CMF or FEC regimens. PCR-RFLP was performed for MTHFR, RFC1 and GSTP1, while PCR for TS, GSTT1 and GSTM1 genes.ResultsAmong the 244 patients consecutively enrolled, 48.7% were treated with FEC and 51.3% with CMF. Patients with TS2R/3R genotype showed less frequently severe neutropenia (G3/G4) than those with TS2R/2R and 3R/3R genotype (p = 0.038). Patients with MTHFRCT genotype had a higher probability of developing severe neutropenia than those with MTHFR CC genotype (p = 0.043). Patients with RFC1GG or GSTT1-null genotype or their combination (GSTT1-null/RFC1GG) were significantly associated with a shorter disease free survival (DFS) (p = 0.009, p = 0.053, p = 0.003, respectively) and overall survival (OS) (p = 0.036, p = 0.015, p = 0.005, respectively). Multivariate analysis confirmed the association of RFC1GG genotype with a shorter DFS (p = 0.018) and of GSTT1-null genotype of a worse OS (p = 0.003), as well as for the combined genotypes GSTT1-null/RFC1GG, (DFS: p = 0.004 and OS: p = 0.003).ConclusionsOur data suggest that TS2R/2R and 3R/3R or MTHFR CT genotypes have a potential role in identifying patients with greater risk of toxicity to CMF/FEC and that RFC1 GG and GSTT1-null genotypes alone or in combination could be important markers in predicting clinical outcome in EBC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3483-2) contains supplementary material, which is available to authorized users.

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