Jose M. C. Tubio

University of Santiago de Compostela | USC · Centro de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS)

Clonally transmissible cancers are tumour lineages that are transmitted between individuals via the transfer of living cancer cells. In marine bivalves, leukaemia-like transmissible cancers, called hemic neoplasia (HN), have demonstrated the ability to infect individuals from different species. We performed whole-genome sequencing in eight warty ve...

Treatment-eradicated cancer subclones have been reported in leukemia and have recently been detected in solid tumors. Here we introduce Differential Subclone Eradication and Resistance (DSER) analysis, a method developed to identify molecular targets for improved therapy by direct comparison of genomic features of eradicated and resistant subclones...

Following its emergence in late 2019, the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1,2 has been tracked via phylogenetic analysis of viral genome sequences in unprecedented detail3–5. While the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, wit...

Most cancers are characterized by the somatic acquisition 52 of genomic rearrangements during tumour evolution that eventually drive the oncogenesis. There are different mutational mechanisms causing structural variation, some of which are specific to particular cancer types. Here, using multiplatform sequencing technologies, we identify and charac...

Resolving genomic structural variation Many human genomes have been reported using short-read technology, but it is difficult to resolve structural variants (SVs) using these data. These genomes thus lack comprehensive comparisons among individuals and populations. Ebert et al. used long-read structural variation calling across 64 human genomes rep...

Long-read and strand-specific sequencing technologies together facilitate the de novo assembly of high-quality haplotype-resolved human genomes without parent–child trio data. We present 64 assembled haplotypes from 32 diverse human genomes. These highly contiguous haplotype assemblies (average contig N50: 26 Mbp) integrate all forms of genetic var...

Regenerative proliferation capacity and poor differentiation are histological features usually linked to poor prognosis in head and neck squamous cell carcinoma (hnSCC). However, the pathways that regulate them remain ill-characterized. Here, we show that those traits can be triggered by the RHO GTPase activator VAV2 in keratinocytes present in the...

Nodal peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) remains a diagnosis encompassing a heterogenous group of PTCL cases not fitting criteria for more homogeneous subtypes. They are characterized by a poor clinical outcome when treated with anthracycline-containing regimens. A better understanding of their biology could improve progn...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole G...

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 1...

Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tum...

The discovery of drivers of cancer has traditionally focused on protein-coding genes1,2,3,4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium⁵ of the International Cancer Genome Consortium (ICGC) and The Cancer Genom...

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG...

A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes1–7. Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of...

The multiple myeloma (MM) genome is heterogeneous and evolves through preclinical and post-diagnosis phases. Here we report a catalog and hierarchy of driver lesions using sequences from 67 MM genomes serially collected from 30 patients together with public exome datasets. Bayesian clustering defines at least 7 genomic subgroups with distinct sets...

Cockles, Cerastoderma edule frequently suffer high prevalence of disseminated neoplasia throughout its geographical distribution. However, a natural population with gonadal neoplasia has never been detected before. Germinoma prevalences of 15.4% were found in Denmark populations using histopathological techniques. This germinoma affects only male c...

Table S3: The 96-Channel Mutational Catalogs of All Samples and Estimated Numbers of Base Substitutions Attributed to Individual Mutational Signatures, Related to Figures 1–6

Table S2: Sample Sets, Data Sources, and Experimental Information, Related to Figures 1–6 List of all samples and the corresponding datasets considered in the study, including previously generated datasets (2,709 primary cancers from Platinum version of the ICGC PCAWG dataset; 1,001 cell lines from COSMIC Cell Line Project; 602 PDX models and avai...

Table S1: Mutational Signatures Used in the Study, Related to Figures 1, 3, 5, and 6 Signatures are displayed based on the probabilities of the 96 substitution classes, defined by the substitution class and sequence context immediately 5′ and 3′ to the mutated base, on the basis of the trinucleotide frequencies of the whole human genome. These inc...

Table S5: Relationships between Mutational Signatures and L1 Retrotransposon Insertions, Related to Figures 4–5 These were examined on available whole-genome sequenced datasets, including 100 cell line daughter/granddaughter clones and 2,353 PCAWG primary cancers. Analysis was performed on complete datasets as listed in Table S2, although only tho...

Table S4: Possibly Deleterious Aberrations in DNA Replication and Repair Mechanisms Associated with Mutational Signatures in Examined Cell Lines, Related to Figures 3 and 4

The recent discovery of clonally transmissible cancers, somatic cell lineages capable of infecting other individuals through the physical transfer of living cells, means having a great model to study cancer metastasis. Disseminated neoplasia, a leukaemia-like cancer is found in multiple bivalve species around the world, including cockles and by ana...

Historically, the differential diagnosis between different nodal peripheral T-cell lymphoma (PTCL) subtypes based on morphological and phenotypic grounds has posed great challenges. In the last few years, our knowledge of the molecular bases of different PTCLs has significantly expanded. However, peripheral T-cell lymphomas not otherwise specified...

DNA methylation is the best studied epigenetic marker, being essential in regulating gene expression and gene silencing in the eukaryotic genome. Different cell types have specific and pre-established DNA methylation profiles according to their organic function. Alterations in this profile may lead to cell malfunction, illness and, ultimately, tumo...

Clonally transmissible cancers are somatic cell lineages transmitted between individuals via the transfer of living cancer cells. There are only three known types of naturally occurring clonally transmissible cancers, one of which is a leukaemia-like cancer found in cockles, called disseminated neoplasia (DN). Using DN as a model to identify the ge...

Cockle Cerastoderma edule is a species of great commercial interest in Galicia, lt is one of the bivalve species with more annual catches and, therefore, has a high economic and ecological importance in this region. Pathological studies associated with cockle mortality events in Galicia detected high prevalence of a pathological condition known as...

Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. Although rare in nature, two facial tumor clones affect Tasmanian devils. Here we perform comparative genetic and functional characterization of these lineages. The two cancers have similar patterns of mutation and show no evidence of exposure to...

Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. Although rare in nature, two facial tumor clones affect Tasmanian devils. Here we perform comparative genetic and functional characterization of these lineages. The two cancers have similar patterns of mutation and show no evidence of exposure to...

Transmissible cancers are somatic cell lineages that spread between individuals via the physical transfer of living cancer cells, becoming able to survive in time through multiple generations due to an unlimited proliferation among host population. To our knowledge, only eight transmissible cancers have been reported in nature. The oldest one of...

La accesibilidad a las técnicas de secuenciación masiva (NGS), hasta hace poco restringidas a estudios de biomedicina, están revolucionando los estudios genéticos. En este estudio se presentan datos preliminares del tamaño del genoma del berberecho Cerastoderma edule, punto de partida para la obtención del genoma de referencia de esta especie. La s...

La accesibilidad a las técnicas de secuenciación masiva (NGS), hasta hace poco restringidas a estudios de biomedicina, están revolucionando los estudios genéticos. En este estudio se presentan datos preliminares del tamaño del genoma del berberecho Cerastoderma edule, punto de partida para la obtención del genoma de referencia de esta especie. La s...

About half of all cancers have somatic integrations of retrotransposons. To characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,774 cancer genomes from 37 histological cancer subtypes. We identified 20,230 somatically acquired retrotransposition events, affecting 43% of samples, and spa...

Anaplastic meningioma is a rare and aggressive brain tumor characterised by intractable recurrences and dismal outcomes. Here, we present an integrated analysis of the whole genome, transcriptome and methylation profiles of primary and recurrent anaplastic meningioma. A key finding was the delineation of two distinct molecular subgroups that were a...

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Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5–15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We aimed to determine the clinical and genetic landscape of those with IGH-CRLF2 or P2RY8-CRLF2 (CRLF2-r) using multiple genomic approaches. Clinical and demographic features of CRLF2-r patients were charact...

Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5-15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We aimed to determine the clinical and genetic landscape of those with IGH-CRLF2 or P2RY8-CRLF2 (CRLF2-r) using multiple genomic approaches. Clinical and demographic features of CRLF2-r patients were charact...

Retrotransposons are repetitive elements that are constantly on the move. By poaching certain enzymes, they copy and insert themselves at new sites in the host genome generating structural variability of potential functional importance for the cancer cell. Retrotransposons can also promote genomic rearrangements by recombination, and mobilize codin...

The authors note that Angela B. Lange should be added to the author list between Leonardo B. Koerich and José Manuel Latorre-Estivalis, and Ian Orchard should be added to the author list between Sheila Ons and Lucia Pagola. Angela B. Lange and Ian Orchard should be credited with supplying sequencing samples and conducting gene annotation and supple...

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-tr...

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-tr...

Supplementary Figures 1-25, Supplementary Tables 1-38, Supplementary Note 1, Supplementary Methods and Supplementary References

Significance Transmissible cancers are somatic cell lineages that are spread between individuals via the transfer of living cancer cells. Only three transmissible cancers have been reported in nature, suggesting that such diseases emerge rarely. One of the known transmissible cancers affects Tasmanian devils, and is threatening this species with ex...