Metastatic cancer remains an almost inevitably lethal disease1–3. A better understanding of disease progression and response to therapies therefore remains of utmost importance. Here we characterize the genomic differences between early-stage untreated primary tumours and late-stage treated metastatic tumours using a harmonized pan-cancer analysis (or reanalysis) of two unpaired primary4 and metastatic5 cohorts of 7,108 whole-genome-sequenced tumours. Metastatic tumours in general have a lower intratumour heterogeneity and a conserved karyotype, displaying only a modest increase in mutations, although frequencies of structural variants are elevated overall. Furthermore, highly variable tumour-specific contributions of mutational footprints of endogenous (for example, SBS1 and APOBEC) and exogenous mutational processes (for example, platinum treatment) are present. The majority of cancer types had either moderate genomic differences (for example, lung adenocarcinoma) or highly consistent genomic portraits (for example, ovarian serous carcinoma) when comparing early-stage and late-stage disease. Breast, prostate, thyroid and kidney renal clear cell carcinomas and pancreatic neuroendocrine tumours are clear exceptions to the rule, displaying an extensive transformation of their genomic landscape in advanced stages. Exposure to treatment further scars the tumour genome and introduces an evolutionary bottleneck that selects for known therapy-resistant drivers in approximately half of treated patients. Our data showcase the potential of pan-cancer whole-genome analysis to identify distinctive features of late-stage tumours and provide a valuable resource to further investigate the biological basis of cancer and resistance to therapies.

Antimicrobial peptides (AMPs) are small, usually cationic, and amphiphilic molecules that play a crucial role in molecular and cellular host defense against pathogens, tissue damage, and infection. AMPs are present in all metazoans and several have been discovered in teleosts. Some teleosts, such as salmonids, have undergone whole genome duplication events and retained a diverse AMP repertoire. Salmonid AMPs have also been shown to possess diverse and potent antibacterial, antiviral, and antiparasitic activity and are induced by a variety of factors, including dietary components and specific molecules also known as pathogen-associated molecular patterns (PAMPs), which may activate downstream signals to initiate transcription of AMP genes. Moreover, a multitude of cell lines have been established from various salmonid species, making it possible to study host-pathogen interactions in vitro, and several of these cell lines have been shown to express various AMPs. In this review, the structure, function, transcriptional regulation, and immunomodulatory role of salmonid AMPs are highlighted in health and disease. It is important to characterize and understand how salmonid AMPs function as this may lead to a better understanding of host-pathogen interactions with implications for aquaculture and medicine.

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