title: Activation of endogenous human stem cell-associated retroviruses (SCARs) and therapy-resistant phenotypes of malignant tumors.
abstract: Recent reports revealed consistent activation of specific endogenous retroviral elements in human preimplantation embryos and embryonic stem cells. Activity of stem cell associated retroviruses (SCARs) has been implicated in seeding thousands of human-specific regulatory sequences in the hESC genome. Activation of specific SCARs has been demonstrated in patients diagnosed with multiple types of cancer, autoimmune diseases, and neurodegenerative disorders, and appears associated with clinically lethal therapy resistant death-from-cancer phenotypes in a sub-set of cancer patients diagnosed with different types of malignant tumors. A hallmark feature of human-specific SCAR integration sites is deletions of ancestral DNA. Analysis of human-specific genetic loci of SCARs' stemness networks in tumor samples of TCGA cohorts representing 29 cancer types suggests that this approach may facilitate identification of pan-cancer genomic signatures of clinically-lethal disease defined by the presence of somatic non-silent mutations, gene-level copy number changes, and transcripts and proteins' expression of SCAR-regulated host genes. Present analyses indicate that multiple lines of strong circumstantial evidence support the hypothesis that activation of SCARs' networks may play an important role in cancer progression and metastasis, perhaps contributing to the emergence of clinically-lethal therapy-resistant death-from-cancer phenotypes.
authors.affiliation: Institute of Engineering in Medicine, University of California, San Diego, 9500 Gilman Dr. MC 0435, La Jolla, CA 92093-0435, USA. Electronic address: gglinskii@ucsd.edu.
authors.forename: Gennadi V
authors.initials: GV
authors.lastname: Glinsky
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D019070:Cell Lineage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D054884:Host-Pathogen Interactions; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D010641:Phenotype; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014775:Virus Activation
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding
keywords: Cancer stem cells; Evolution of modern humans; Human embryos; Human endogenous stem cell-associated retroviruses (SCARs); Human-specific regulatory sequences; Therapy-resistant cancers; hESC