Transposable elements and Cancer

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Transposable elements and Cancer 유전체정보연구실 이희은 2016.10.11

Transposable elements B. Chénais / Biochimica et Biophysica Acta 1835 (2013) 28–35

Transposable elements in the human genome - Cordaux , et al., Nat Rev Genet. 2009 Oct; 10(10): 691–703. - Lander, E.S., et al., Nature, 2001. 409(6822): 860-921. - Repeatmakser (www.repeatmasker.org/) - Our work (Not published)

Impact of retrotransposons on human genome structure a | Typical insertion of an L1, Alu or SVA retrotransposon (red box) at a new genomic site (blue area). If the new genomic site is a genic region, the retrotransposon may cause insertional mutagenesis.  b | The protein products of an L1 element (red circle) may create DNA double-strand breaks (broken blue area). Alternatively, an existing double-strand break may be repaired via non-classical endonuclease-independent insertion of a retrotransposon (red box).  c | Microsatellites (e.g. (TA)n) may arise from the homopolymeric tracts endogenous to retrotransposons.  d | Gene conversion may alter the sequence compositions of homologous retrotransposon copies (red and green boxes).  e | Insertion of retrotransposons (red box) is sometimes associated with concomittant deletion of target genomic sequences (light blue box).  f | Ectopic recombination (double arrowheaded line) between non-allelic homologous retrotransposons (red boxes) may result in genomic reaarangements such as deletions (left) or duplications (right) of intervening genomic sequences.  g | 3′ and 5′ transduction can result in the co-retrotransposition of downstream or upstream flanking genomic sequence, respectively, along with a retrotransposon (left and right, respectively). - Cordaux , et al., Nat Rev Genet. 2009 Oct; 10(10): 691–703.

Impact of retrotransposons on human gene expression a | Typical insertion of an L1, Alu or SVA retrotransposon (red box) at a new genomic site (blue area). If the new genomic site is a genic region, the retrotransposon may cause insertional mutagenesis.  b | The protein products of an L1 element (red circle) may create DNA double-strand breaks (broken blue area). Alternatively, an existing double-strand break may be repaired via non-classical endonuclease-independent insertion of a retrotransposon (red box).  c | Microsatellites (e.g. (TA)n) may arise from the homopolymeric tracts endogenous to retrotransposons.  d | Gene conversion may alter the sequence compositions of homologous retrotransposon copies (red and green boxes). e | Insertion of retrotransposons (red box) is sometimes associated with concomittant deletion of target genomic sequences (light blue box).  f | Ectopic recombination (double arrowheaded line) between non-allelic homologous retrotransposons (red boxes) may result in genomic reaarangements such as deletions (left) or duplications (right) of intervening genomic sequences.  g | 3′ and 5′ transduction can result in the co-retrotransposition of downstream or upstream flanking genomic sequence, respectively, along with a retrotransposon (left and right, respectively). - Cordaux , et al., Nat Rev Genet. 2009 Oct; 10(10): 691–703.

Transposable elements in various cells Trends in Genetics Vol.26 No.6

Retrotransposon-derived p53 binding sites P. M. Lieberman. Bioessays 38: 943–949, 2016.

Retrotransposon-derived p53 binding sites P. M. Lieberman. Bioessays 38: 943–949, 2016.

Human Endogenous Retroviruses (HERVs)

Human Endogenous Retroviruses (HERVs) gag pro pol env Provirus U3 R U5 5’LTR 3’LTR Full length Transcripts Transcription AAAA PBS Translation SU (Surface subunit) TM (Transmembrane subunit) Human Chimpanzee Gorilla Orangutan Gibbon Old World monkeys New World monkeys Prosimians 70 60 50 40 30 20 10 Million years HERV-K HERV-W HERV-E/PTN HERV-L HERV-P HERV-H HERV-FRD HERV-F HERV-M HERV-E HERV-I HERV-R ERV-9 HERV-H10,18,19 HERV-H/E hybrid HERV-H/PLA2L

Environmental factors and HERVs Cancer Yolken et al., Brain Res., 2000. HERVs Chemicals Microbes Hormones Cytokines Aberrant Expression Indirect Insertional mutagenesis Dysregulation Direct Superantigens Immunosuppression Toxicity

HERVs and tumor related Cancer biology and Medicine sep. 22. 2016

HERVs and inflammatory diseases

Transposable elements associated with Cancer B. Chénais / Biochimica et Biophysica Acta 1835 (2013) 28–35

HERV associated with Cancer Mol Biol. Volume 5. issue 3

HERV associated with Cancer Mol Biol. Volume 5. issue 3

Researches on TE and cancer Oncotarget august 11, 2016.

Researches on TE and cancer I.V. Gainetdinov et al. / Lung Cancer 99 (2016) 127–130

Future perspective of Cancer and Transposable elements Oncogene (2003) 22, 1528–1535.

Summary and References Links between Human INE-1 retrotransposons and hepatitis Virus-related hepatocellular carcinoma. Honda T. May 2016. Volume 4. article 21. Hypomethylation of human-specific family of LINE-1 retrotransposons in circulating DNA of lung cancer patients. Gainetdinov et al. 99: 2016. 127-130. Human dndogenous retroviruses and cancer. Gonzalez et al. 22. sep. 2016. unpublished. Retrotransposons-derived p53 binding sites enhance telomere maintenanace and genome protection. Liberman PM. Bioessays 38: 943-949. Meeting Report: The Role of the Mobilome in Cancer. Ardeljan et al. Cancer Res; 76(15) August 1, 2016. Quantitation of HERV-K env gene expression and splicing in human breast cancer. Wang-Johanning et al. oncogene 2003. 22: 1528-1535. The Role of Human Endogenous Retroviruses (HERV-K) in the Pathogenesis of Human Cancers. Simmons, Mol Biol 2016, 5:3. Variable Transcriptional Activity of Endogenous Retroviruses in Human Breast Cancer. JOURNAL OF VIROLOGY, Feb. 2008, p. 1808–1818. Transposable elements and human cancer: A causal relationship? Biochimica et Biophysica Acta 1835 (2013) 28–35