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Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features

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Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features. / Lessel, Davor; Vaz, Bruno; Halder, Swagata; Lockhart, Paul J; Marinovic-Terzic, Ivana; Lopez-Mosqueda, Jaime; Philipp, Melanie; Sim, Joe C H; Smith, Katherine R; Oehler, Judith; Cabrera, Elisa; Freire, Raimundo; Pope, Kate; Nahid, Amsha; Norris, Fiona; Leventer, Richard J; Delatycki, Martin B; Barbi, Gotthold; von Ameln, Simon; Högel, Josef; Degoricija, Marina; Fertig, Regina; Burkhalter, Martin D; Hofmann, Kay; Thiele, Holger; Altmüller, Janine; Nürnberg, Gudrun; Nürnberg, Peter; Bahlo, Melanie; Martin, George M; Aalfs, Cora M; Oshima, Junko; Terzic, Janos; Amor, David J; Dikic, Ivan; Ramadan, Kristijan; Kubisch, Christian.

in: NAT GENET, Jahrgang 46, Nr. 11, 01.11.2014, S. 1239-44.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Lessel, D, Vaz, B, Halder, S, Lockhart, PJ, Marinovic-Terzic, I, Lopez-Mosqueda, J, Philipp, M, Sim, JCH, Smith, KR, Oehler, J, Cabrera, E, Freire, R, Pope, K, Nahid, A, Norris, F, Leventer, RJ, Delatycki, MB, Barbi, G, von Ameln, S, Högel, J, Degoricija, M, Fertig, R, Burkhalter, MD, Hofmann, K, Thiele, H, Altmüller, J, Nürnberg, G, Nürnberg, P, Bahlo, M, Martin, GM, Aalfs, CM, Oshima, J, Terzic, J, Amor, DJ, Dikic, I, Ramadan, K & Kubisch, C 2014, 'Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features', NAT GENET, Jg. 46, Nr. 11, S. 1239-44. https://doi.org/10.1038/ng.3103

APA

Lessel, D., Vaz, B., Halder, S., Lockhart, P. J., Marinovic-Terzic, I., Lopez-Mosqueda, J., Philipp, M., Sim, J. C. H., Smith, K. R., Oehler, J., Cabrera, E., Freire, R., Pope, K., Nahid, A., Norris, F., Leventer, R. J., Delatycki, M. B., Barbi, G., von Ameln, S., ... Kubisch, C. (2014). Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features. NAT GENET, 46(11), 1239-44. https://doi.org/10.1038/ng.3103

Vancouver

Lessel D, Vaz B, Halder S, Lockhart PJ, Marinovic-Terzic I, Lopez-Mosqueda J et al. Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features. NAT GENET. 2014 Nov 1;46(11):1239-44. https://doi.org/10.1038/ng.3103

Bibtex

@article{72393c886d784050a7bc6d5c97a2c985,
title = "Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features",
abstract = "Age-related degenerative and malignant diseases represent major challenges for health care systems. Elucidation of the molecular mechanisms underlying carcinogenesis and age-associated pathologies is thus of growing biomedical relevance. We identified biallelic germline mutations in SPRTN (also called C1orf124 or DVC1) in three patients from two unrelated families. All three patients are affected by a new segmental progeroid syndrome characterized by genomic instability and susceptibility toward early onset hepatocellular carcinoma. SPRTN was recently proposed to have a function in translesional DNA synthesis and the prevention of mutagenesis. Our in vivo and in vitro characterization of identified mutations has uncovered an essential role for SPRTN in the prevention of DNA replication stress during general DNA replication and in replication-related G2/M-checkpoint regulation. In addition to demonstrating the pathogenicity of identified SPRTN mutations, our findings provide a molecular explanation of how SPRTN dysfunction causes accelerated aging and susceptibility toward carcinoma.",
keywords = "Age of Onset, Animals, Base Sequence, Carcinoma, Hepatocellular, Chromosome Mapping, Cloning, Molecular, DNA Primers, DNA Replication, DNA-Binding Proteins, Flow Cytometry, Fluorescent Antibody Technique, Genes, cdc, Genomic Instability, Germ-Line Mutation, Humans, Liver Neoplasms, Male, Molecular Sequence Data, Pedigree, Progeria, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Zebrafish",
author = "Davor Lessel and Bruno Vaz and Swagata Halder and Lockhart, {Paul J} and Ivana Marinovic-Terzic and Jaime Lopez-Mosqueda and Melanie Philipp and Sim, {Joe C H} and Smith, {Katherine R} and Judith Oehler and Elisa Cabrera and Raimundo Freire and Kate Pope and Amsha Nahid and Fiona Norris and Leventer, {Richard J} and Delatycki, {Martin B} and Gotthold Barbi and {von Ameln}, Simon and Josef H{\"o}gel and Marina Degoricija and Regina Fertig and Burkhalter, {Martin D} and Kay Hofmann and Holger Thiele and Janine Altm{\"u}ller and Gudrun N{\"u}rnberg and Peter N{\"u}rnberg and Melanie Bahlo and Martin, {George M} and Aalfs, {Cora M} and Junko Oshima and Janos Terzic and Amor, {David J} and Ivan Dikic and Kristijan Ramadan and Christian Kubisch",
year = "2014",
month = nov,
day = "1",
doi = "10.1038/ng.3103",
language = "English",
volume = "46",
pages = "1239--44",
journal = "NAT GENET",
issn = "1061-4036",
publisher = "NATURE PUBLISHING GROUP",
number = "11",

}

RIS

TY - JOUR

T1 - Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features

AU - Lessel, Davor

AU - Vaz, Bruno

AU - Halder, Swagata

AU - Lockhart, Paul J

AU - Marinovic-Terzic, Ivana

AU - Lopez-Mosqueda, Jaime

AU - Philipp, Melanie

AU - Sim, Joe C H

AU - Smith, Katherine R

AU - Oehler, Judith

AU - Cabrera, Elisa

AU - Freire, Raimundo

AU - Pope, Kate

AU - Nahid, Amsha

AU - Norris, Fiona

AU - Leventer, Richard J

AU - Delatycki, Martin B

AU - Barbi, Gotthold

AU - von Ameln, Simon

AU - Högel, Josef

AU - Degoricija, Marina

AU - Fertig, Regina

AU - Burkhalter, Martin D

AU - Hofmann, Kay

AU - Thiele, Holger

AU - Altmüller, Janine

AU - Nürnberg, Gudrun

AU - Nürnberg, Peter

AU - Bahlo, Melanie

AU - Martin, George M

AU - Aalfs, Cora M

AU - Oshima, Junko

AU - Terzic, Janos

AU - Amor, David J

AU - Dikic, Ivan

AU - Ramadan, Kristijan

AU - Kubisch, Christian

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Age-related degenerative and malignant diseases represent major challenges for health care systems. Elucidation of the molecular mechanisms underlying carcinogenesis and age-associated pathologies is thus of growing biomedical relevance. We identified biallelic germline mutations in SPRTN (also called C1orf124 or DVC1) in three patients from two unrelated families. All three patients are affected by a new segmental progeroid syndrome characterized by genomic instability and susceptibility toward early onset hepatocellular carcinoma. SPRTN was recently proposed to have a function in translesional DNA synthesis and the prevention of mutagenesis. Our in vivo and in vitro characterization of identified mutations has uncovered an essential role for SPRTN in the prevention of DNA replication stress during general DNA replication and in replication-related G2/M-checkpoint regulation. In addition to demonstrating the pathogenicity of identified SPRTN mutations, our findings provide a molecular explanation of how SPRTN dysfunction causes accelerated aging and susceptibility toward carcinoma.

AB - Age-related degenerative and malignant diseases represent major challenges for health care systems. Elucidation of the molecular mechanisms underlying carcinogenesis and age-associated pathologies is thus of growing biomedical relevance. We identified biallelic germline mutations in SPRTN (also called C1orf124 or DVC1) in three patients from two unrelated families. All three patients are affected by a new segmental progeroid syndrome characterized by genomic instability and susceptibility toward early onset hepatocellular carcinoma. SPRTN was recently proposed to have a function in translesional DNA synthesis and the prevention of mutagenesis. Our in vivo and in vitro characterization of identified mutations has uncovered an essential role for SPRTN in the prevention of DNA replication stress during general DNA replication and in replication-related G2/M-checkpoint regulation. In addition to demonstrating the pathogenicity of identified SPRTN mutations, our findings provide a molecular explanation of how SPRTN dysfunction causes accelerated aging and susceptibility toward carcinoma.

KW - Age of Onset

KW - Animals

KW - Base Sequence

KW - Carcinoma, Hepatocellular

KW - Chromosome Mapping

KW - Cloning, Molecular

KW - DNA Primers

KW - DNA Replication

KW - DNA-Binding Proteins

KW - Flow Cytometry

KW - Fluorescent Antibody Technique

KW - Genes, cdc

KW - Genomic Instability

KW - Germ-Line Mutation

KW - Humans

KW - Liver Neoplasms

KW - Male

KW - Molecular Sequence Data

KW - Pedigree

KW - Progeria

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Sequence Analysis, DNA

KW - Zebrafish

U2 - 10.1038/ng.3103

DO - 10.1038/ng.3103

M3 - SCORING: Journal article

C2 - 25261934

VL - 46

SP - 1239

EP - 1244

JO - NAT GENET

JF - NAT GENET

SN - 1061-4036

IS - 11

ER -