Oesophageal adenocarcinoma (OAC) provides an ideal case study to characterize large-scale rearrangements. Using whole genome short-read sequencing of 383 cases, for which 214 had matched whole transcriptomes, we observed structural variations (SV) with a predominance of deletions, tandem duplications and inter-chromosome junctions that could be identified as LINE-1 mobile element (ME) insertions. Complex clusters of rearrangements resembling breakage-fusion-bridge cycles or extrachromosomal circular DNA accounted for 22% of complex SVs affecting known oncogenes. Counting SV events affecting known driver genes substantially increased the recurrence rates of these drivers. After excluding fragile sites, we identified 51 candidate new drivers in genomic regions disrupted by SVs, including ETV5, KAT6B and CLTC. RUNX1 was the most recurrently altered gene (24%), with many deletions inactivating the RUNT domain but preserved the reading frame, suggesting an altered protein product. These findings underscore the importance of identification of SV events in OAC with implications for targeted therapies.
Global declines in shorebird populations resulting from foraging habitat loss have been recently reported, and the situation within the East Asian-Australasian Flyway (EAAF) is particularly concerning. Despite previous studies that analyzed the foraging niches of shorebirds worldwide, the dietary niche dynamics of shorebirds coexisting in Asia are very poorly understood. This study is therefore among the early few that aim to unveil the trophic organization of shorebirds in a subtropical wetland within the EAAF which is vital for species conservation. Our study first determined the dietary spectra of more than 10 shorebird species, such as Calidris ferruginea (near threatened), Charadrius leschenaultii, and Pluvialis squatarola, by applying DNA metabarcoding with 18S and COI markers to fecal DNA. The diet of Tringa stagnatilis was also characterized, which was previously undescribed. Shorebirds that occurred in the wetland consumed a variety of food items, primarily a high abundance of malacostracans, mollusks, annelids, insects, and some arachnids. Different proportions of plant materials were also detected in many shorebird species. Using the data, we then revealed clear patterns of inter-and intraspecific variations between these shorebirds. Importantly, we specifically compared the similarities of the spring diets among seven sympatric shorebird species. We found that the dietary compositions of the seven species have segregated from each other to varying levels, but the many similar taxa we identified in the diets among these shorebirds imply that these populations of shorebirds could be competing at different levels. Thus, any reductions in the abundance and diversity of these important food resources would likely intensify their inter-and intraspecific competition, and simultaneously threaten the survival of multiple species. With these findings, conservation measures must be taken to protect and monitor the vital food resources for these energy-deprived shorebirds during migration.
A variety of mutational processes drive cancer development, but their dynamics across the entire disease spectrum from pre-cancerous to advanced neoplasia are poorly understood. We explore the mutagenic processes shaping oesophageal adenocarcinoma tumorigenesis in 997 instances comprising distinct stages of this malignancy, from Barrett Oesophagus to primary tumours and advanced metastatic disease. The mutational landscape is dominated by the C[T > C/G]T substitution enriched signatures SBS17a/b, which are linked with TP53 mutations, increased proliferation, genomic instability and disease progression. The APOBEC mutagenesis signature is a weak but persistent signal amplified in primary tumours. We also identify prevalent alterations in DNA damage repair pathways, with homologous recombination, base and nucleotide excision repair and translesion synthesis mutated in up to 50% of the cohort, and surprisingly uncoupled from transcriptional activity. Among these, the presence of base excision repair deficiencies show remarkably poor prognosis in the cohort. In this work, we provide insights on the mutational aetiology and changes enabling the transition from pre-neoplastic to advanced oesophageal adenocarcinoma.
Throughout the Plio-Pleistocene, climate change has impacted tropical marine ecosystems substantially, with even more severe impacts predicted in the Anthropocene. Although many studies have clarified demographic histories of seabirds in polar regions, the history of keystone seabirds of the tropics is unclear, despite the prominence of albatrosses (Diomedeidae, Procellariiformes) as the largest and most threatened group of oceanic seabirds. To understand the impact of climate change on tropical albatrosses, we investigated the evolutionary and demographic histories of all four North Pacific albatrosses and their prey using whole-genome analyses. We report a striking concordance in demographic histories among the four species, with a notable dip in effective population size at the beginning of the Pleistocene and a population expansion in the Last Glacial Period when sea levels were low, which resulted in increased potential coastal breeding sites. Abundance of the black-footed albatross dropped again during the Last Glacial Maximum, potentially linked to climate-driven loss of breeding sites and concordant genome-derived decreases in its major prey. We find very low genome-wide (π < 0.001) and adaptative genetic diversities across the albatrosses, with genes of the major histocompatibility complex close to monomorphic. We also identify recent selective sweeps at genes associated with hyperosmotic adaptation, longevity, and cognition and memory. Our study has shed light on the evolutionary and demographic histories of the largest tropical oceanic seabirds and provides evidence for their large population fluctuations and alarmingly low genetic diversities.
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