Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.

Spectrometers with ever-smaller footprints are sought after for a wide range of applications in which minimized size and weight are paramount, including emerging in situ characterization techniques. We report on an ultracompact microspectrometer design based on a single compositionally engineered nanowire. This platform is independent of the complex optical components or cavities that tend to constrain further miniaturization of current systems. We show that incident spectra can be computationally reconstructed from the different spectral response functions and measured photocurrents along the length of the nanowire. Our devices are capable of accurate, visible-range monochromatic and broadband light reconstruction, as well as spectral imaging from centimeter-scale focal planes down to lensless, single-cell–scale in situ mapping.

Summary PTEN is one of the most frequently mutated genes in human cancer. It is known that PTEN has a wide range of biological functions beyond tumor suppression. Here we report that PTENα, an N-terminally extended form of PTEN, functions in metabolism. Translation of PTENα is initiated from a CUG codon upstream of and in-frame with the coding region of canonical PTEN. Eukaryotic translation initiation factor 2A (eIF2A) controls PTENα translation and a CUG-centered palindromic motif is required in this process. PTENα induces cytochrome c oxidase activity and ATP production in mitochondria. TALEN-mediated somatic deletion of PTENα impairs mitochondrial respiratory chain function. We show that PTENα interacts with canonical PTEN to increase PINK1 and promote energy production. These data provide insights into the mechanism by which the PTEN family is involved in multiple cellular processes. Our studies suggest that mammalian cells can use alternate translation initiation mechanisms to generate protein isoforms.

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