High BRAF variant allele frequencies are associated with distinct pathological features and responsiveness to target therapy in melanoma patients.

BACKGROUND: BRAF mutant melanoma patients are commonly treated with anti-BRAF therapeutic strategies. However, many factors, including the percentage of BRAF-mutated cells, may contribute to the great variability in patient outcomes. PATIENTS AND METHODS: The BRAF variant allele frequency (VAF; defined as the percentage of mutated alleles) of primary and secondary melanoma lesions, obtained from 327 patients with different disease stages, was assessed by pyrosequencing. The BRAF mutation rate and VAF were then correlated with melanoma pathological features and patients' clinical characteristics. Kaplan-Meier curves were used to study the correlations between BRAF VAF, overall survival (OS), and progression-free survival (PFS) in a subset of 62 patients treated by anti-BRAF/anti-MEK therapy after metastatic progression. RESULTS: A highly heterogeneous BRAF VAF was identified (3%-90%). Besides being correlated with age, a higher BRAF VAF level was related to moderate lymphocytic infiltration (P = 0.017), to melanoma thickness according to Clark levels, (level V versus III, P = 0.004; level V versus IV, P = 0.04), to lymph node metastases rather than cutaneous (P = 0.04) or visceral (P = 0.03) secondary lesions. In particular, a BRAF VAF >25% was significantly associated with a favorable outcome in patients treated with the combination of anti-BRAF/anti-MEK drug (OS P = 0.04; PFS P = 0.019), retaining a significant value as an independent factor for the OS and the PFS in the multivariate analysis (P = 0.014 and P = 0.003, respectively). CONCLUSION: These results definitively support the role of the BRAF VAF as a potential prognostic and predictive biomarker in melanoma patients in the context of BRAF inhibition.

Detecting bit-flip errors in a logical qubit using stabilizer measurements.

Quantum data are susceptible to decoherence induced by the environment and to errors in the hardware processing it. A future fault-tolerant quantum computer will use quantum error correction to actively protect against both. In the smallest error correction codes, the information in one logical qubit is encoded in a two-dimensional subspace of a larger Hilbert space of multiple physical qubits. For each code, a set of non-demolition multi-qubit measurements, termed stabilizers, can discretize and signal physical qubit errors without collapsing the encoded information. Here using a five-qubit superconducting processor, we realize the two parity measurements comprising the stabilizers of the three-qubit repetition code protecting one logical qubit from physical bit-flip errors. While increased physical qubit coherence times and shorter quantum error correction blocks are required to actively safeguard the quantum information, this demonstration is a critical step towards larger codes based on multiple parity measurements.

Universal quantum gate set approaching fault-tolerant thresholds with superconducting qubits.

We use quantum process tomography to characterize a full universal set of all-microwave gates on two superconducting single-frequency single-junction transmon qubits. All extracted gate fidelities, including those for Clifford group generators, single-qubit π/4 and π/8 rotations, and a two-qubit controlled-not, exceed 95% (98%), without (with) subtracting state preparation and measurement errors. Furthermore, we introduce a process map representation in the Pauli basis which is visually efficient and informative. This high-fidelity gate set serves as a critical building block towards scalable architectures of superconducting qubits for error correction schemes and pushes up on the known limits of quantum gate characterization.

Characterization of addressability by simultaneous randomized benchmarking.

The control and handling of errors arising from cross talk and unwanted interactions in multiqubit systems is an important issue in quantum information processing architectures. We introduce a benchmarking protocol that provides information about the amount of addressability present in the system and implement it on coupled superconducting qubits. The protocol consists of randomized benchmarking experiments run both individually and simultaneously on pairs of qubits. A relevant figure of merit for the addressability is then related to the differences in the measured average gate fidelities in the two experiments. We present results from two similar samples with differing cross talk and unwanted qubit-qubit interactions. The results agree with predictions based on simple models of the classical cross talk and Stark shifts.

Entanglement of two superconducting qubits in a waveguide cavity via monochromatic two-photon excitation.

We report a system where fixed interactions between noncomputational levels make bright the otherwise forbidden two-photon |00}→|11} transition. The system is formed by hand selection and assembly of two discrete component transmon-style superconducting qubits inside a rectangular microwave cavity. The application of a monochromatic drive tuned to this transition induces two-photon Rabi-like oscillations between the ground and doubly excited states via the Bell basis. The system therefore allows all-microwave two-qubit universal control with the same techniques and hardware required for single qubit control. We report Ramsey-like and spin echo sequences with the generated Bell states, and measure a two-qubit gate fidelity of F(g)=90% (unconstrained) and 86% (maximum likelihood estimator).