Biphenotypic sinonasal sarcoma: European multicentre case-series and systematic literature review

Objective. Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade cancer that was included from the 4th edition of WHO classification of head and neck tumours. The purpose of this study is to analyse clinical behaviour, pattern of recurrences and survival outcomes of this neoplasm. Methods. Retrospective review of patients affected by BSNS who were treated via an en-doscopic-assisted approach in 6 European tertiary-care referral hospitals. Cases of BSNS described in literature since 2012 to date were fully reviewed, according to PRISMA guide-lines. Results. A total of 15 patients were included. Seven patients were treated via an endoscopic endonasal approach, 4 with endoscopic transnasal craniectomy, and 4 via a cranio-endoscopic approach. Adjuvant treatment was delivered in 2 cases. After a mean follow-up of 27.3 months, systemic metastasis was observed in 1 case; the 5-year overall survival and disease-free survival rates were 100% and 80 ± 17.9%, respectively. Conclusions. BSNS is a locally aggressive tumour with a low recurrence rate and encour-aging survival outcomes if properly treated with surgical resection and free margins fol-lowed by adjuvant radiotherapy for selected cases. Endoscopic-assisted surgery is safe and effective as an upfront treatment within a multidisciplinary care protocol

Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors.

BACKGROUND: Human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) is an emerging disease, representing a distinct clinical and epidemiological entity. Understanding the genetic basis of this specific subtype of cancer could allow therapeutic targeting of affected pathways for a stratified medicine approach. METHODS: Twenty HPV+ and 20 HPV- laser-capture microdissected oropharyngeal carcinomas were used for paired-end sequencing of hybrid-captured DNA, targeting 3,230 exons in 182 genes often mutated in cancer. Copy number alteration (CNA) profiling, Sequenom MassArray sequencing and immunohistochemistry were used to further validate findings. RESULTS: HPV+ and HPV- oropharyngeal carcinomas cluster into two distinct subgroups. TP53 mutations are detected in 100% of HPV negative cases and abrogation of the G1/S checkpoint by CDKN2A/B deletion and/or CCND1 amplification occurs in the majority of HPV- tumors. CONCLUSION: These findings strongly support a causal role for HPV, acting via p53 and RB pathway inhibition, in the pathogenesis of a subset of oropharyngeal cancers and suggest that studies of CDK inhibitors in HPV negative disease may be warranted. Mutation and copy number alteration of PI3 kinase (PI3K) pathway components appears particularly prevalent in HPV+ tumors and assessment of these alterations may aid in the interpretation of current clinical trials of PI3K, AKT and mTOR inhibitors in HNSCC

Identification and functional validation of HPV-mediated hypermethylation in head and neck squamous cell carcinoma.

ABSTRACT: BACKGROUND: Human Papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) represents a distinct clinical and epidemiological entity compared with HPV negative (HPV-) HNSCC. To test the possible involvement of epigenetic modulation by HPV in HNSCC, we conducted a genome-wide DNA methylation analysis. METHODS: Using laser-capture microdissection of 42 formalin-fixed paraffin-embedded (FFPE) HNSCCs, we generated DNA methylation profiles of 18 HPV+ and 14 HPV- samples, using the Infinium 450k BeadArray technology. Methylation data were validated in two sets of independent HPV+/HPV- HNSCC samples (fresh frozen and cell lines) using two independent methods (Infinium 450k and whole-genome MeDIP-seq). For the functional analysis, an HPV- HNSCC cell line was transduced with lentiviral constructs containing the two HPV oncogenes (E6 and E7) and effects on methylation were assayed using the Infinium 450k technology. RESULTS AND DISCUSSION: Unsupervised clustering over the most methylation variable positions (MVPs) showed that samples segregated according to HPV status, but also that HPV+ tumours are heterogeneous. MVPs were significantly enriched at transcriptional start sites, leading to the identification of a candidate CpG Island Methylator Phenotype in a sub-group of the HPV+ tumours. Supervised analysis revealed a strong preponderance (87%) of MVPs towards hypermethylation in HPV+ HNSCC. Meta-analysis of our HNSCC and publicly available methylation data in cervical and lung cancer confirmed the observed DNA methylation signature to be HPV-specific and tissue-independent. Grouping of MVPs into functionally more significant differentially methylated regions (DMRs) identified 43 hypermethylated promoter DMRs, including for three Cadherins of the Polycomb group target genes. Integration with independent expression data showed strong negative correlation, especially for the Cadherin gene family members. Combinatorial ectopic expression of the two HPV oncogenes (E6 and E7) in an HPV- HNSCC cell line partially phenocopied the hypermethylation signature observed in HPV+ HNSCC tumours and established E6 as the main viral effector gene. CONCLUSIONS: Our data establish archival FFPE tissue to be highly suitable for this type of methylome analysis and suggest that HPV modulates the HNSCC epigenome through hypermethylation of Polycomb repressive complex 2 target genes such as Cadherins which are implicated in tumour progression and metastasis

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV

The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe

Development and validation of HERWIG 7 tunes from CMS underlying-event measurements

This paper presents new sets of parameters (“tunes”) for the underlying-event model of the HERWIG7 event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in HERWIG7, and are obtained from a fit to minimum-bias data collected by the CMS experiment at s=0.9, 7, and 13Te. The tunes are based on the NNPDF 3.1 next-to-next-to-leading-order parton distribution function (PDF) set for the parton shower, and either a leading-order or next-to-next-to-leading-order PDF set for the simulation of MPI and the beam remnants. Predictions utilizing the tunes are produced for event shape observables in electron-positron collisions, and for minimum-bias, inclusive jet, top quark pair, and Z and W boson events in proton-proton collisions, and are compared with data. Each of the new tunes describes the data at a reasonable level, and the tunes using a leading-order PDF for the simulation of MPI provide the best description of the dat

Measurement of B-c(2S)(+) and B-c*(2S)(+) cross section ratios in proton-proton collisions at root s=13 TeV

Peer reviewe

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV