Assessment of three epigenotypes in colorectal cancer by combined bisulphite restriction analysis.

Background: Recent investigations have demonstrated the clear heterogeneity of sporadic colorectal cancer (CRC) with regard to CpG island methylation. Two unsupervised cluster analyses revealed that CRCs form three distinct DNA methylation subsets, which are referred to as the high-, intermediate- and low-methylation epigenotypes (HME, IME, and LME, respectively). A recent study by Yagi et al. found a fairly sensitive and specific identification of HME, IME and LME using two marker panels analysed by MALDI-TOF mass spectrometry (MassARRAY). However, the expensive equipment required for this method substantially increases the cost and complexity of the assay. Findings: In this article, we demonstrate the assessment of HME, IME and LME in a group of 233 sporadic CRCs using seven markers proposed by Yagi et al. The DNA methylation of each marker was quantified using combined bisulphite restriction analysis (COBRA) together with an analysis of various genetic factors associated with CRC (the BRAF and KRAS mutations and microsatellite instability (MSI)). The baseline methylation of each marker was generated from pooled DNA isolated from 50 normal colon tissues. Conclusions: We demonstrate that the correlation of HME, IME and LME epigenotyped by COBRA using different molecular classifiers is similar to that achieved by MassARRAY. Therefore, epigenotyping CRCs using COBRA is a simple, specific and cost-effective method that has the potential to be widely used in CRC research

Electrical Switch to the Resonant Magneto-Phonon Effect in Graphene

We report a comprehensive study of the tuning with electric fields of the resonant magneto-exciton optical phonon coupling in gated graphene. For magnetic fields around <i>B</i> ∼ 25 T that correspond to the range of the fundamental magneto-phonon resonance, the electron–phonon coupling can be switched on and off by tuning the position of the Fermi level in order to Pauli block the two fundamental inter-Landau level excitations. The effects of such a profound change in the electronic excitation spectrum are traced through investigations of the optical phonon response in polarization resolved magneto-Raman scattering experiments. We report on the observation of a splitting of the phonon feature with satellite peaks developing at particular values of the Landau level filling factor on the low or on the high energy side of the phonon, depending on the relative energy of the discrete electronic excitation and of the optical phonon. Shifts of the phonon energy as large as ±60 cm^–1 are observed close to the resonance. The intraband electronic excitation, the cyclotron resonance, is shown to play a relevant role in the observed spectral evolution of the phonon response