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Abstract Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy after hepatocellular carcinoma, with poor prognosis and limited treatment options. The genomic features of ICC in Chinese patients remain largely unknown. In this study, we perform deep whole-exome sequencing of 204 Chinese primary ICCs and characterize genomic alterations and clonal evolution, and reveal their associations with patient outcomes. We identify six mutational signatures, including Signatures A and F, which are highly similar to previously described signatures linked to aristolochic acid and aflatoxin exposures, respectively. We also identify 13 significantly mutated genes in the ICC samples, including SAV1. We find that SAV1 was mutated in 2.9% (20/672) of 672 ICC samples. SAV1 mutation is associated with lower SAV1 protein levels, higher rates of tumor recurrence, and shorter overall patient survival. Biofunctional investigations reveal a tumor-suppressor role of SAV1: its inactivation suppresses Hippo signaling, leading to YAP activation, thereby promoting tumor growth and metastasis. Collectively, our results delineate the genomic landscape of Chinese ICCs and identify SAV1 as a potential driver of ICC.

Abstract Patients with hepatocellular carcinoma (HCC) have poor long-term survival following curative resection because of the high rate of tumor early recurrence. Little is known about the trajectory of genomic evolution from primary to early-recurrent HCC. In this study, we performed whole-genome sequencing (WGS) on 40 pairs of primary and early-recurrent hepatitis B virus (HBV)-related HCC tumors from patients who received curative resection, and from four patients whose primary and recurrent tumor were extensively sampled. We identified two recurrence patterns: de novo recurrence (18/40), which developed genetically independently of the primary tumor and carried different HCC drivers, and ancestral recurrence (22/40), which was clonally related to the primary tumor and progressed more rapidly than de novo recurrence. We found that the recurrence location was predictive of the recurrence pattern: distant recurrence tended to display the de novo pattern, whereas local recurrence tended to display the ancestral pattern. We then uncovered the evolutionary trajectories based on the subclonal architecture, driver-gene mutations, and mutational processes observed in the primary and recurrent tumors. Multi-region WGS demonstrated spatiotemporal heterogeneity and polyclonal, monophyletic dissemination in HCC ancestral recurrence. In addition, we identified recurrence-specific mutations and copy-number gains in BCL9, leading to WNT/β-catenin signaling activation and an immune-excluded tumor microenvironment, which suggests that BCL9 might serve as a new therapeutic target for recurrent HCC. Collectively, our results allow us to view with unprecedented clarity the genomic evolution during HBV-related HCC early recurrence, providing an important molecular foundation for enhanced understanding of HCC with implications for personalized therapy to improve patient survival.

In the title compound, C30H38O4S2, the centroid of the benzene ring lies on a center of inversion. The thiophene ring is aligned at 49.8 (1)° with respect to the benzene ring. The alkyl chain adopts an extended zigzag conformation.

We report the fabrication of simply structured and high performance organic complementary inverters based on an ambipolar organic semiconductor, 8,9,10,11-tetrachloro-6,13-bis-(triisopropylsilylethynyl)-1-azapentacene (4Cl-Azapen). Individual transistors using symmetric Au electrodes showed high and balanced performance, with good hole (up to 0.23 cm2V−1s−1) and electron (up to 0.21 cm2V−1s−1) mobilities. Integrated complementary inverters showed sharp inversions with high gains (>180) and negligible hysteresis. The inverters using low-cost electrodes, Ag and Cu, also exhibited high gains and high noise margins (>75% of the ideal value).

A strategy is described for designing high-performance, ambipolar, acene-based field-effect transistor (FET) materials, which is based on the replacement of C-H moieties by nitrogen atoms in oligoacenes. The demonstration of high and balanced ambipolar FET properties from nitrogen-containing oligoacenes has provided new opportunities for designing high-performance ambipolar organic semiconductors.

The tribe Oryzeae consists of 12 genera and 71 species with a world distribution. Zizania latifolia (Griseb.) Turcz. ex Stapf is included in this tribe and possesses numerous traits valuable for rice breeding, such as disease and insect resistance, cold and flood tolerance, and high grain quality. The genetics and breeding of Z. latifolia are still in their infancy. To facilitate genomic studies of Zizania, a genomic DNA library was constructed using a transformation-competent artificial chromosome (TAC) vector system. The TAC library contains 91, 584 TAC clones with an average insert size of approximately 45 kb, covering six haploid Zizania genome equivalents. Very low signals after hybridization with chloroplast and mitochondrial genes indicate that the TAC library is predominantly composed of nuclear DNA. The TAC clones were stable in E. coli for 100 generations. Clones containing the dihydrodipicolinate synthase (DHPS) gene were screened by pooled PCR. The positive clones can be used for Z. latifolia DHPS gene cloning and functional analysis. The library will be useful in studies of genome structure, gene cloning and evolution of rice. [ABSTRACT FROM AUTHOR]