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      Malignant Transformation of Hymenolepis nana in a Human Host.

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          Abstract

          Neoplasms occur naturally in invertebrates but are not known to develop in tapeworms. We observed nests of monomorphic, undifferentiated cells in samples from lymph-node and lung biopsies in a man infected with the human immunodeficiency virus (HIV). The morphologic features and invasive behavior of the cells were characteristic of cancer, but their small size suggested a nonhuman origin. A polymerase-chain-reaction (PCR) assay targeting eukaryotes identified Hymenolepis nana DNA. Although the cells were unrecognizable as tapeworm tissue, immunohistochemical staining and probe hybridization labeled the cells in situ. Comparative deep sequencing identified H. nana structural genomic variants that are compatible with mutations described in cancer. Invasion of human tissue by abnormal, proliferating, genetically altered tapeworm cells is a novel disease mechanism that links infection and cancer.

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          High-resolution mapping of copy-number alterations with massively parallel sequencing.

          Derek Y Chiang, Gad Getz, David B. Jaffe … (2009)
          Cancer results from somatic alterations in key genes, including point mutations, copy-number alterations and structural rearrangements. A powerful way to discover cancer-causing genes is to identify genomic regions that show recurrent copy-number alterations (gains and losses) in tumor genomes. Recent advances in sequencing technologies suggest that massively parallel sequencing may provide a feasible alternative to DNA microarrays for detecting copy-number alterations. Here we present: (i) a statistical analysis of the power to detect copy-number alterations of a given size; (ii) SegSeq, an algorithm to segment equal copy numbers from massively parallel sequence data; and (iii) analysis of experimental data from three matched pairs of tumor and normal cell lines. We show that a collection of approximately 14 million aligned sequence reads from human cell lines has comparable power to detect events as the current generation of DNA microarrays and has over twofold better precision for localizing breakpoints (typically, to within approximately 1 kilobase).
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            Somatic mutations of the mitochondrial genome in human colorectal tumours.

            Kornelia Polyak, Yunbo Li, Hong Zhu … (1998)
            Alterations of oxidative phosphorylation in tumour cells were originally believed to have a causative role in cancerous growth. More recently, mitochondria have again received attention with regards to neoplasia, largely because of their role in apoptosis and other aspects of tumour biology. The mitochondrial genome is particularly susceptible to mutations because of the high level of reactive oxygen species (ROS) generation in this organelle, coupled with a low level of DNA repair. However, no detailed analysis of mitochondrial DNA in human tumours has yet been reported. In this study, we analysed the complete mtDNA genome of ten human colorectal cancer cell lines by sequencing and found mutations in seven (70%). The majority of mutations were transitions at purines, consistent with an ROS-related derivation. The mutations were somatic, and those evaluated occurred in the primary tumour from which the cell line was derived. Most of the mutations were homoplasmic, indicating that the mutant genome was dominant at the intracellular and intercellular levels. We showed that mitochondria can rapidly become homogeneous in colorectal cancer cells using cell fusions. These findings provide the first examples of homoplasmic mutations in the mtDNA of tumour cells and have potential implications for the abnormal metabolic and apoptotic processes in cancer.
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              Landscape of somatic retrotransposition in human cancers.

              Eunjung Lee, Rebecca Cheryl Iskow, Lixing Yang … (2012)
              Transposable elements (TEs) are abundant in the human genome, and some are capable of generating new insertions through RNA intermediates. In cancer, the disruption of cellular mechanisms that normally suppress TE activity may facilitate mutagenic retrotranspositions. We performed single-nucleotide resolution analysis of TE insertions in 43 high-coverage whole-genome sequencing data sets from five cancer types. We identified 194 high-confidence somatic TE insertions, as well as thousands of polymorphic TE insertions in matched normal genomes. Somatic insertions were present in epithelial tumors but not in blood or brain cancers. Somatic L1 insertions tend to occur in genes that are commonly mutated in cancer, disrupt the expression of the target genes, and are biased toward regions of cancer-specific DNA hypomethylation, highlighting their potential impact in tumorigenesis.
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                Author and article information

                Journal
                Journal ID (iso-abbrev): N. Engl. J. Med.
                Title: The New England journal of medicine
                Publisher: New England Journal of Medicine (NEJM/MMS)
                ISSN (Electronic): 1533-4406
                ISSN (Print): 0028-4793
                Publication date (Electronic): Nov 05 2015
                Volume: 373
                Issue: 19
                Affiliations
                [1 ] From the Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (A.M., J.B., M.G.M., D.C.R., T.L.J., P.W.G., S.R.Z.), Parasitic Diseases Branch, Division of Parasitic Diseases and Malaria, Center for Global Health (M.L.E., B.A.M.), Biotechnology Core Facility, Division of Scientific Resources, National Center for Emerging and Zoonotic Infectious Diseases (M.A.F.), Waterborne Disease Prevention Branch, Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases (G.S.V.), and Mycotic Diseases Branch (C.D.P.), Centers for Disease Control and Prevention (CDC), and Emory University School of Medicine (A.H.) - all in Atlanta; Universidad Pontificia Bolivariana School of Health Sciences (C.A.A., A.H., A.V.H., L.R.D.), Clínica Universitaria Bolivariana (C.A.A.), and Hospital Pablo Tobón Uribe (A.H., A.V.H.), Medellín, and Centros Especializados de San Vicente Fundación, Rionegro (C.A.A.) - all in Colombia; Asahikawa Medical University, Asahikawa, Japan (A.I.); and the Department of Life Sciences, Division of Parasites and Vectors, Natural History Museum, London (P.D.O.).
                Article
                DOI: 10.1056/NEJMoa1505892
                PubMed ID: 26535513
                SO-VID: eef903dc-33a8-4cc9-861c-fe8e008318b7
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