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2. Sex-dependent dominance maintains migration supergene in rainbow trout

Author

Pearse, Devon E., Barson, Nicola J., Nome, Torfinn, Gao, Guangtu, Campbell, Matthew A., Abadía-Cardoso, Alicia, Anderson, Eric C., Rundio, David E., Williams, Thomas H., Naish, Kerry A., Moen, Thomas, Liu, Sixin, Kent, Matthew, Moser, Michel, Minkley, David R., Rondeau, Eric B., Brieuc, Marine S. O., Sandve, Simen Rød, Miller, Michael R., Cedillo, Lucydalila, Baruch, Kobi, Hernandez, Alvaro G., Ben-Zvi, Gil, Shem-Tov, Doron, Barad, Omer, Kuzishchin, Kirill, Garza, John Carlos, Lindley, Steven T., Koop, Ben F., Thorgaard, Gary H., Palti, Yniv, and Lien, Sigbjørn

Published
2019
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3. The structural variation landscape in 492 Atlantic salmon genomes

Author

Bertolotti, Alicia C., Layer, Ryan M., Gundappa, Manu Kumar, Gallagher, Michael D., Pehlivanoglu, Ege, Nome, Torfinn, Robledo, Diego, Kent, Matthew P., Røsæg, Line L., Holen, Matilde M., Mulugeta, Teshome D., Ashton, Thomas J., Hindar, Kjetil, Sægrov, Harald, Florø-Larsen, Bjørn, Erkinaro, Jaakko, Primmer, Craig R., Bernatchez, Louis, Martin, Samuel A. M., Johnston, Ian A., Sandve, Simen R., Lien, Sigbjørn, and Macqueen, Daniel J.

Published
2020
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4. Supplemental Materials, Figures S1-6, Tables S1-4 from Regulator of Chromosome Condensation 2 Identifies High-Risk Patients within Both Major Phenotypes of Colorectal Cancer

Author

Bruun, Jarle, primary, Kolberg, Matthias, primary, Ahlquist, Terje C., primary, Røyrvik, Ellen C., primary, Nome, Torfinn, primary, Leithe, Edward, primary, Lind, Guro E., primary, Merok, Marianne A., primary, Rognum, Torleiv O., primary, Bjørkøy, Geir, primary, Johansen, Terje, primary, Lindblom, Annika, primary, Sun, Xiao-Feng, primary, Svindland, Aud, primary, Liestøl, Knut, primary, Nesbakken, Arild, primary, Skotheim, Rolf I., primary, and Lothe, Ragnhild A., primary

Published
2023
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6. Publisher Correction: Sex-dependent dominance maintains migration supergene in rainbow trout

Author

Pearse, Devon E., Barson, Nicola J., Nome, Torfinn, Gao, Guangtu, Campbell, Matthew A., Abadía-Cardoso, Alicia, Anderson, Eric C., Rundio, David E., Williams, Thomas H., Naish, Kerry A., Moen, Thomas, Liu, Sixin, Kent, Matthew, Moser, Michel, Minkley, David R., Rondeau, Eric B., Brieuc, Marine S. O., Sandve, Simen Rød, Miller, Michael R., Cedillo, Lucydalila, Baruch, Kobi, Hernandez, Alvaro G., Ben-Zvi, Gil, Shem-Tov, Doron, Barad, Omer, Kuzishchin, Kirill, Garza, John Carlos, Lindley, Steven T., Koop, Ben F., Thorgaard, Gary H., Palti, Yniv, and Lien, Sigbjørn

Published
2020
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7. The Atlantic salmon genome provides insights into rediploidization

Author

Lien, Sigbjørn, Koop, Ben F., Sandve, Simen R., Miller, Jason R., Kent, Matthew P., Nome, Torfinn, Hvidsten, Torgeir R., Leong, Jong S., Minkley, David R., Zimin, Aleksey, Grammes, Fabian, Grove, Harald, Gjuvsland, Arne, Walenz, Brian, Hermansen, Russell A., von Schalburg, Kris, Rondeau, Eric B., Di Genova, Alex, Samy, Jeevan K. A., Olav Vik, Jon, Vigeland, Magnus D., Caler, Lis, Grimholt, Unni, Jentoft, Sissel, Inge Våge, Dag, de Jong, Pieter, Moen, Thomas, Baranski, Matthew, Palti, Yniv, Smith, Douglas R., Yorke, James A., Nederbragt, Alexander J., Tooming-Klunderud, Ave, Jakobsen, Kjetill S., Jiang, Xuanting, Fan, Dingding, Hu, Yan, Liberles, David A., Vidal, Rodrigo, Iturra, Patricia, Jones, Steven J. M., Jonassen, Inge, Maass, Alejandro, Omholt, Stig W., and Davidson, William S.

Published
2016
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8. Sex-dependent dominance at a single locus maintains variation in age at maturity in salmon

Author

Barson, Nicola J., Aykanat, Tutku, Hindar, Kjetil, Baranski, Matthew, Bolstad, Geir H., Fiske, Peder, Jacq, Celeste, Jensen, Arne J., Johnston, Susan E., Karlsson, Sten, Kent, Matthew, Moen, Thomas, Niemela, Eero, Nome, Torfinn, Naesje, Tor F., Orell, Panu, Romakkaniemi, Atso, Saegrov, Harald, Urdal, Kurt, Erkinaro, Jaakko, Lien, Sigbjorn, and Primmer, Craig R.

Subjects
Genomics -- Research, Evolution -- Research, Salmon -- Research -- Genetic aspects, Single nucleotide polymorphisms -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Males and females share many traits that have a common genetic basis; however, selection on these traits often differs between the sexes, leading to sexual conflict (1,2). Under such sexual antagonism, theory predicts the evolution of genetic architectures that resolve this sexual conflict (2-5). Yet, despite intense theoretical and empirical interest, the specific loci underlying sexually antagonistic phenotypes have rarely been identified, limiting our understanding of how sexual conflict impacts genome evolution (3,6) and the maintenance of genetic diversity (6,7). Here we identify a large effect locus controlling age at maturity in Atlantic salmon (Salmo salar), an important fitness trait in which selection favours earlier maturation in males than females (8), and show it is a clear example of sex-dependent dominance that reduces intralocus sexual conflict and maintains adaptive variation in wild populations. Using high-density single nucleotide polymorphism data across 57 wild populations and whole genome re-sequencing, we find that the vestigial-like family member 3 gene (VGLL3) exhibits sex-dependent dominance in salmon, promoting earlier and later maturation in males and females, respectively. VGLL3, an adiposity regulator associated with size and age at maturity in humans, explained 39% of phenotypic variation, an unexpectedly large proportion for what is usually considered a highly polygenic trait. Such large effects are predicted under balancing selection from either sexually antagonistic or spatially varying selection (9,10). Our results provide the first empirical example of dominance reversal allowing greater optimization of phenotypes within each sex, contributing to the resolution of sexual conflict in a major and widespread evolutionary trade-off between age and size at maturity. They also provide key empirical evidence for how variation in reproductive strategies can be maintained over large geographical scales. We anticipate these findings will have a substantial impact on population management in a range of harvested species where trends towards earlier maturation have been observed., The importance of balancing selection in maintaining variation in fitness-related traits, which are expected to be under strong selection, is a long-standing question in evolutionary biology (7,11,12), with recent models [...]

Published
2015

15. The structural variation landscape in 492 Atlantic salmon genomes

Author

Bertolotti, Alicia C., primary, Layer, Ryan M., additional, Gundappa, Manu Kumar, additional, Gallagher, Michael D., additional, Pehlivanoglu, Ege, additional, Nome, Torfinn, additional, Robledo, Diego, additional, Kent, Matthew P., additional, Røsæg, Line L., additional, Holen, Matilde M., additional, Mulugeta, Teshome D., additional, Ashton, Thomas J., additional, Hindar, Kjetil, additional, Sægrov, Harald, additional, Florø-Larsen, Bjørn, additional, Erkinaro, Jaakko, additional, Primmer, Craig R., additional, Bernatchez, Louis, additional, Martin, Samuel A.M., additional, Johnston, Ian A., additional, Sandve, Simen R., additional, Lien, Sigbjørn, additional, and Macqueen, Daniel J., additional

Published
2020
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16. Publisher Correction: Sex-dependent dominance maintains migration supergene in rainbow trout

Author

Pearse, Devon E., primary, Barson, Nicola J., additional, Nome, Torfinn, additional, Gao, Guangtu, additional, Campbell, Matthew A., additional, Abadía-Cardoso, Alicia, additional, Anderson, Eric C., additional, Rundio, David E., additional, Williams, Thomas H., additional, Naish, Kerry A., additional, Moen, Thomas, additional, Liu, Sixin, additional, Kent, Matthew, additional, Moser, Michel, additional, Minkley, David R., additional, Rondeau, Eric B., additional, Brieuc, Marine S. O., additional, Sandve, Simen Rød, additional, Miller, Michael R., additional, Cedillo, Lucydalila, additional, Baruch, Kobi, additional, Hernandez, Alvaro G., additional, Ben-Zvi, Gil, additional, Shem-Tov, Doron, additional, Barad, Omer, additional, Kuzishchin, Kirill, additional, Garza, John Carlos, additional, Lindley, Steven T., additional, Koop, Ben F., additional, Thorgaard, Gary H., additional, Palti, Yniv, additional, and Lien, Sigbjørn, additional

Published
2019
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18. Additional file 1: of SalMotifDB: a tool for analyzing putative transcription factor binding sites in salmonid genomes

Author

Teshome Mulugeta, Nome, Torfinn, Thu-Hien To, Gundappa, Manu, Macqueen, Daniel, VĂĽge, Dag, Sandve, Simen, and Hvidsten, Torgeir

Abstract

Figure S1. A radial tree displaying the similarity structure of a selected motif cluster. The inner node represent the cluster name (cluster-393), nodes in the second layer represent the motif databases, the third layer represent motif/TF names and the outer layer represent consensus motifs (not available for TRANSFAC). The central motifs of each motif database cluster are highlighted in red. (PDF 260 kb)

Published
2019
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20. Additional file 2: Table S1. of CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extension

Author

Celestino, Ricardo, Nome, Torfinn, Pestana, Ana, Hoff, Andreas M., A. Pedro Gonçalves, Pereira, Luísa, Cavadas, Bruno, Eloy, Catarina, Bjøro, Trine, Sobrinho-Simões, Manuel, Skotheim, Rolf I., and Soares, Paula

Subjects
endocrine system
Abstract

Genes differentially expressed between minimally (mFTC) and widely invasive follicular thyroid carcinoma (wFTC). (DOCX 14 kb)

Published
2018
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21. Additional file 12: Table S6. of CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extension

Author

Celestino, Ricardo, Nome, Torfinn, Pestana, Ana, Hoff, Andreas M., A. Pedro Gonçalves, Pereira, Luísa, Cavadas, Bruno, Eloy, Catarina, Bjøro, Trine, Sobrinho-Simões, Manuel, Skotheim, Rolf I., and Soares, Paula

Abstract

Clinicopathological and genetic data of the FTC classified by classes based on gene expression. (DOCX 18 kb)

Published
2018
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22. Additional file 8: of CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extension

Author

Celestino, Ricardo, Nome, Torfinn, Pestana, Ana, Hoff, Andreas M., A. Pedro Gonçalves, Pereira, Luísa, Cavadas, Bruno, Eloy, Catarina, Bjøro, Trine, Sobrinho-Simões, Manuel, Skotheim, Rolf I., and Soares, Paula

Subjects
endocrine system
Abstract

Prediction and experimental validation of the fusion genes expressed in follicular thyroid carcinomas used in RNA-sequencing. (DOCX 17 kb)

Published
2018
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23. Additional file 7: Table S4. of CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extension

Author

Celestino, Ricardo, Nome, Torfinn, Pestana, Ana, Hoff, Andreas M., A. Pedro Gonçalves, Pereira, Luísa, Cavadas, Bruno, Eloy, Catarina, Bjøro, Trine, Sobrinho-Simões, Manuel, Skotheim, Rolf I., and Soares, Paula

Abstract

Oligonucleotide primers used in RT-PCR to detect the fusion genes. (DOCX 13 kb)

Published
2018
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24. Additional file 6: Table S3. of CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extension

Author

Celestino, Ricardo, Nome, Torfinn, Pestana, Ana, Hoff, Andreas M., A. Pedro Gonçalves, Pereira, Luísa, Cavadas, Bruno, Eloy, Catarina, Bjøro, Trine, Sobrinho-Simões, Manuel, Skotheim, Rolf I., and Soares, Paula

Subjects
endocrine system
Abstract

Fusion genes selected by customized filtering steps and experimentally validated by RT-PCR and Sanger sequencing. FTC, follicular thyroid carcinoma; ORF, open reading frame. (DOCX 15 kb)

Published
2018
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25. Additional file 3: Table S2. of CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extension

Author

Celestino, Ricardo, Nome, Torfinn, Pestana, Ana, Hoff, Andreas M., A. Pedro Gonçalves, Pereira, Luísa, Cavadas, Bruno, Eloy, Catarina, Bjøro, Trine, Sobrinho-Simões, Manuel, Skotheim, Rolf I., and Soares, Paula

Subjects
endocrine system
Abstract

Transcripts differentially expressed between minimally (mFTC) and widely invasive follicular thyroid carcinoma (wFTC). (DOCX 14 kb)

Published
2018
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26. Additional file 1: of CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extension

Author

Celestino, Ricardo, Nome, Torfinn, Pestana, Ana, Hoff, Andreas M., A. Pedro Gonçalves, Pereira, Luísa, Cavadas, Bruno, Eloy, Catarina, Bjøro, Trine, Sobrinho-Simões, Manuel, Skotheim, Rolf I., and Soares, Paula

Abstract

Clinicopathological features and genetic alterations of the differentiated thyroid carcinoma (DTC) series. (DOCX 12 kb)

Published
2018
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27. Sex-dependent dominance maintains migration supergene in rainbow trout

Author

Pearse, Devon E., primary, Barson, Nicola J., additional, Nome, Torfinn, additional, Gao, Guangtu, additional, Campbell, Matthew A., additional, Abadía-Cardoso, Alicia, additional, Anderson, Eric C., additional, Rundio, David E., additional, Williams, Thomas H., additional, Naish, Kerry A., additional, Moen, Thomas, additional, Liu, Sixin, additional, Kent, Matthew, additional, Minkley, David R., additional, Rondeau, Eric B., additional, Brieuc, Marine S. O., additional, Rød Sandve, Simen, additional, Miller, Michael R., additional, Cedillo, Lucydalila, additional, Baruch, Kobi, additional, Hernandez, Alvaro G., additional, Ben-Zvi, Gil, additional, Shem-Tov, Doron, additional, Barad, Omer, additional, Kuzishchin, Kirill, additional, Garza, John Carlos, additional, Lindley, Steven T., additional, Koop, Ben F., additional, Thorgaard, Gary H., additional, Palti, Yniv, additional, and Lien, Sigbjørn, additional

Published
2018
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28. Casein haplotypes and their association with milk production traits in Norwegian Red cattle

Author

Nome Torfinn, Svendsen Morten, Sehested Erling, Hayes Ben, Olsen Hanne, Nilsen Heidi, Meuwissen Theo, and Lien Sigbjørn

Subjects
Animal culture, SF1-1100, Genetics, QH426-470
Abstract

Abstract A high resolution SNP map was constructed for the bovine casein region to identify haplotype structures and study associations with milk traits in Norwegian Red cattle. Our analyses suggest separation of the casein cluster into two haplotype blocks, one consisting of the CSN1S1, CSN2 and CSN1S2 genes and another one consisting of the CSN3 gene. Highly significant associations with both protein and milk yield were found for both single SNPs and haplotypes within the CSN1S1-CSN2-CSN1S2 haplotype block. In contrast, no significant association was found for single SNPs or haplotypes within the CSN3 block. Our results point towards CSN2 and CSN1S2 as the most likely loci harbouring the underlying causative DNA variation. In our study, the most significant results were found for the SNP CSN2_67 with the C allele consistently associated with both higher protein and milk yields. CSN2_67 calls a C to an A substitution at codon 67 in β-casein gene resulting in histidine replacing proline in the amino acid sequence. This polymorphism determines the protein variants A1/B (CSN2_67 A allele) versus A2/A3 (CSN2_67 C allele). Other studies have suggested that a high consumption of A1/B milk may affect human health by increasing the risk of diabetes and heart diseases. Altogether these results argue for an increase in the frequency of the CSN2_67 C allele or haplotypes containing this allele in the Norwegian Red cattle population by selective breeding.

Published
2009
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30. Evolution of Sex Determination Loci in Atlantic Salmon

Author

Kijas, James, primary, McWilliam, Sean, additional, Naval Sanchez, Marina, additional, Kube, Peter, additional, King, Harry, additional, Evans, Bradley, additional, Nome, Torfinn, additional, Lien, Sigbjørn, additional, and Verbyla, Klara, additional

Published
2018
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31. Erratum

Author

Kirubakaran, Tina Graceline, primary, Grove, Harald, additional, Kent, Matthew P., additional, Sandve, Simen R., additional, Baranski, Matthew, additional, Nome, Torfinn, additional, De Rosa, Maria Cristina, additional, Righino, Benedetta, additional, Johansen, Torild, additional, Otterå, Håkon, additional, Sonesson, Anna, additional, Lien, Sigbjø Rn, additional, and Andersen, Øivind, additional

Published
2018
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32. CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extension

Author

Celestino, Ricardo, primary, Nome, Torfinn, additional, Pestana, Ana, additional, Hoff, Andreas M., additional, Gonçalves, A. Pedro, additional, Pereira, Luísa, additional, Cavadas, Bruno, additional, Eloy, Catarina, additional, Bjøro, Trine, additional, Sobrinho-Simões, Manuel, additional, Skotheim, Rolf I., additional, and Soares, Paula, additional

Published
2018
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33. MOESM2 of Fine mapping of a QTL on bovine chromosome 6 using imputed full sequence data suggests a key role for the group-specific component (GC) gene in clinical mastitis and milk production

Author

Olsen, Hanne, Knutsen, Tim, Lewandowska-Sabat, Anna, Grove, Harald, Nome, Torfinn, Svendsen, Morten, Arnyasi, Mariann, Sodeland, Marte, Kristil Sundsaasen, Dahl, Sandra, BjøRg Heringstad, Hansen, Hanne, Olsaker, Ingrid, Kent, Matthew, and SigbjøRn Lien

Abstract

Additional file 2: Table S2. Primer sequences used for the reverse transcription qPCR (RT-qPCR).

Published
2016
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35. Genome-wide association mapping for milk fat composition and fine mapping of a QTL for de novo synthesis of milk fatty acids on bovine chromosome 13

Author

Olsen, Hanne Gro, primary, Knutsen, Tim Martin, additional, Kohler, Achim, additional, Svendsen, Morten, additional, Gidskehaug, Lars, additional, Grove, Harald, additional, Nome, Torfinn, additional, Sodeland, Marte, additional, Sundsaasen, Kristil Kindem, additional, Kent, Matthew Peter, additional, Martens, Harald, additional, and Lien, Sigbjørn, additional

Published
2017
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36. Unscrambling the genomic chaos of osteosarcoma reveals extensive transcript fusion, recurrent rearrangements and frequent novel TP53 aberrations

Author

Lorenz, Susanne, Baroy, Tale, Sun, Jinchang, Nome, Torfinn, Vodak, Daniel, Bryne, Jan-Christian, Hakelien, Anne-Mari, Fernandez-Cuesta, Lynnette, Moehlendick, Birte, Rieder, Harald, Szuhai, Karoly, Zaikova, Olga, Ahlquist, Terje C., Thomassen, Gard O. S., Skotheim, Rolf I., Lothe, Ragnhild A., Tarpey, Patrick S., Campbell, Peter, Flanagan, Adrienne, Myklebost, Ola, Meza-Zepeda, Leonardo A., Lorenz, Susanne, Baroy, Tale, Sun, Jinchang, Nome, Torfinn, Vodak, Daniel, Bryne, Jan-Christian, Hakelien, Anne-Mari, Fernandez-Cuesta, Lynnette, Moehlendick, Birte, Rieder, Harald, Szuhai, Karoly, Zaikova, Olga, Ahlquist, Terje C., Thomassen, Gard O. S., Skotheim, Rolf I., Lothe, Ragnhild A., Tarpey, Patrick S., Campbell, Peter, Flanagan, Adrienne, Myklebost, Ola, and Meza-Zepeda, Leonardo A.

Abstract

In contrast to many other sarcoma subtypes, the chaotic karyotypes of osteosarcoma have precluded the identification of pathognomonic translocations. We here report hundreds of genomic rearrangements in osteosarcoma cell lines, showing clear characteristics of microhomology-mediated break-induced replication (MMBIR) and end-joining repair (MMEJ) mechanisms. However, at RNA level, the majority of the fused transcripts did not correspond to genomic rearrangements, suggesting the involvement of trans-splicing, which was further supported by typical trans-splicing characteristics. By combining genomic and transcriptomic analysis, certain recurrent rearrangements were identified and further validated in patient biopsies, including a PMP22-ELOVL5 gene fusion, genomic structural variations affecting RB1, MTAP/CDKN2A and MDM2, and, most frequently, rearrangements involving TP53. Most cell lines (7/11) and a large fraction of tumor samples (10/25) showed TP53 rearrangements, in addition to somatic point mutations (6 patient samples, 1 cell line) and MDM2 amplifications (2 patient samples, 2 cell lines). The resulting inactivation of p53 was demonstrated by a deficiency of the radiation-induced DNA damage response. Thus, TP53 rearrangements are the major mechanism of p53 inactivation in osteosarcoma. Together with active MMBIR and MMEJ, this inactivation probably contributes to the exceptional chromosomal instability in these tumors. Although rampant rearrangements appear to be a phenotype of osteosarcomas, we demonstrate that among the huge number of probable passenger rearrangements, specific recurrent, possibly oncogenic, events are present. For the first time the genomic chaos of osteosarcoma is characterized so thoroughly and delivered new insights in mechanisms involved in osteosarcoma development and may contribute to new diagnostic and therapeutic strategies.

Published
2016

37. Fine mapping of a QTL on bovine chromosome 6 using imputed full sequence data suggests a key role for the group-specific component (GC) gene in clinical mastitis and milk production

Author

Olsen, Hanne Gro, primary, Knutsen, Tim Martin, additional, Lewandowska-Sabat, Anna M., additional, Grove, Harald, additional, Nome, Torfinn, additional, Svendsen, Morten, additional, Arnyasi, Mariann, additional, Sodeland, Marte, additional, Sundsaasen, Kristil K., additional, Dahl, Sandra Rinne, additional, Heringstad, Bjørg, additional, Hansen, Hanne H., additional, Olsaker, Ingrid, additional, Kent, Matthew Peter, additional, and Lien, Sigbjørn, additional

Published
2016
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38. Two adjacent inversions maintain genomic differentiation between migratory and stationary ecotypes of Atlantic cod

Author

Kirubakaran, Tina Graceline, primary, Grove, Harald, additional, Kent, Matthew P., additional, Sandve, Simen R., additional, Baranski, Matthew, additional, Nome, Torfinn, additional, De Rosa, Maria Cristina, additional, Righino, Benedetta, additional, Johansen, Torild, additional, Otterå, Håkon, additional, Sonesson, Anna, additional, Lien, Sigbjørn, additional, and Andersen, Øivind, additional

Published
2016
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39. Regulator of Chromosome Condensation 2 Identifies High-Risk Patients within Both Major Phenotypes of Colorectal Cancer

Author

Bruun, Jarle, Kolberg, Matthias, Ahlquist, Terje C., Royrvik, Ellen C., Nome, Torfinn, Leithe, Edward, Lind, Guro E., Merok, Marianne A., Rognum, Torleiv O., Bjorkoy, Geir, Johansen, Terje, Lindblom, Annika, Sun, Xiao-Feng, Svindland, Aud, Liestol, Knut, Nesbakken, Arild, Skotheim, Rolf I., Lothe, Ragnhild A., Bruun, Jarle, Kolberg, Matthias, Ahlquist, Terje C., Royrvik, Ellen C., Nome, Torfinn, Leithe, Edward, Lind, Guro E., Merok, Marianne A., Rognum, Torleiv O., Bjorkoy, Geir, Johansen, Terje, Lindblom, Annika, Sun, Xiao-Feng, Svindland, Aud, Liestol, Knut, Nesbakken, Arild, Skotheim, Rolf I., and Lothe, Ragnhild A.

Abstract

Purpose: Colorectal cancer has high incidence and mortality worldwide. Patients with microsatellite instable (MSI) tumors have significantly better prognosis than patients with microsatellite stable (MSS) tumors. Considerable variation in disease outcome remains a challenge within each subgroup, and our purpose was to identify biomarkers that improve prediction of colorectal cancer prognosis. Experimental Design: Mutation analyses of 42 MSI target genes were performed in two independent MSI tumor series (n = 209). Markers that were significantly associated with prognosis in the test series were assessed in the validation series, followed by functional and genetic explorations. The clinical potential was further investigated by immunohistochemistry in a population-based colorectal cancer series (n = 903). Results: We identified the cell-cycle gene regulator of chromosome condensation 2 (RCC2) as a cancer biomarker. We found a mutation in the 50 UTR region of RCC2 that in univariate and multivariate analyses was significantly associated with improved outcome in the MSI group. This mutation caused reduction of protein expression in dual luciferase gene reporter assays. siRNA knockdown in MSI colon cancer cells (HCT15) caused reduced cell proliferation, cell-cycle arrest, and increased apoptosis. Massive parallel sequencing revealed few RCC2 mutations in MSS tumors. However, weak RCC2 protein expression was significantly associated with poor prognosis, independent of clinical highrisk parameters, and stratifies clinically important patient subgroups with MSS tumors, including elderly patients (greater than 75 years), stage II patients, and those with rectal cancer. Conclusions: Impaired RCC2 affects functional and clinical endpoints of colorectal cancer. High-risk patients with either MSI or MSS tumors can be identified with cost-effective routine RCC2 assays. (C) 2015 AACR., Funding Agencies|Norwegian Cancer Society [PR-2006-0442, PR-2007-0166]; South-Eastern Norway Regional Health Authority

Published
2015
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40. Unscrambling the genomic chaos of osteosarcoma reveals extensive transcript fusion, recurrent rearrangements and frequent novel TP53 aberrations

Author

Lorenz, Susanne, primary, Barøy, Tale, additional, Sun, Jinchang, additional, Nome, Torfinn, additional, Vodák, Daniel, additional, Bryne, Jan-Christian, additional, Håkelien, Anne-Mari, additional, Fernandez-Cuesta, Lynnette, additional, Möhlendick, Birte, additional, Rieder, Harald, additional, Szuhai, Karoly, additional, Zaikova, Olga, additional, Ahlquist, Terje C., additional, Thomassen, Gard O. S., additional, Skotheim, Rolf I., additional, Lothe, Ragnhild A., additional, Tarpey, Patrick S., additional, Campbell, Peter, additional, Flanagan, Adrienne, additional, Myklebost, Ola, additional, and Meza-Zepeda, Leonardo A., additional

Published
2015
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41. Novel RNA variants in colorectal cancers

Author

Hoff, Andreas M., primary, Johannessen, Bjarne, additional, Alagaratnam, Sharmini, additional, Zhao, Sen, additional, Nome, Torfinn, additional, Løvf, Marthe, additional, Bakken, Anne C., additional, Hektoen, Merete, additional, Sveen, Anita, additional, Lothe, Ragnhild A., additional, and Skotheim, Rolf I., additional

Published
2015
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42. Sex-dependent dominance at a single locus maintains variation in age at maturity in Atlantic salmon

Author

Barson, Nicola J, primary, Aykanat, Tutku, additional, Hindar, Kjetil, additional, Baranski, Matthew, additional, Bolstad, Geir H, additional, Fiske, Peder, additional, Jacq, Celeste, additional, Jensen, Arne, additional, Johnston, Susan E, additional, Karlsoon, Sten, additional, Kent, Matthew, additional, Niemelä, Eero, additional, Nome, Torfinn, additional, Naesje, Tor F, additional, Orell, Panu, additional, Romakkaniemi, Atso, additional, Saegrov, Harald, additional, Urdal, Kurt, additional, Erkinaro, Jaakko, additional, Lien, Sigbjørn, additional, and Primmer, Craig R, additional

Published
2015
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43. Regulator of Chromosome Condensation 2 Identifies High-Risk Patients within Both Major Phenotypes of Colorectal Cancer

Author

Bruun, Jarle, primary, Kolberg, Matthias, additional, Ahlquist, Terje C., additional, Røyrvik, Ellen C., additional, Nome, Torfinn, additional, Leithe, Edward, additional, Lind, Guro E., additional, Merok, Marianne A., additional, Rognum, Torleiv O., additional, Bjørkøy, Geir, additional, Johansen, Terje, additional, Lindblom, Annika, additional, Sun, Xiao-Feng, additional, Svindland, Aud, additional, Liestøl, Knut, additional, Nesbakken, Arild, additional, Skotheim, Rolf I., additional, and Lothe, Ragnhild A., additional

Published
2015
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45. A novel transcript,VNN1-AB, as a biomarker for colorectal cancer

Author

Løvf, Marthe, primary, Nome, Torfinn, additional, Bruun, Jarle, additional, Eknaes, Mette, additional, Bakken, Anne C., additional, Mpindi, John P., additional, Kilpinen, Sami, additional, Rognum, Torleiv O., additional, Nesbakken, Arild, additional, Kallioniemi, Olli, additional, Lothe, Ragnhild A., additional, and Skotheim, Rolf I., additional

Published
2014
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47. Common Fusion Transcripts Identified in Colorectal Cancer Cell Lines by High-Throughput RNA Sequencing

Author

Nome, Torfinn, primary, Thomassen, Gard O.S., additional, Bruun, Jarle, additional, Ahlquist, Terje, additional, Bakken, Anne C., additional, Hoff, Andreas M., additional, Rognum, Torleiv, additional, Nesbakken, Arild, additional, Lorenz, Susanne, additional, Sun, Jinchang, additional, Barros-Silva, João Diogo, additional, Lind, Guro E., additional, Myklebost, Ola, additional, Teixeira, Manuel R., additional, Meza-Zepeda, Leonardo A., additional, Lothe, Ragnhild A., additional, and Skotheim, Rolf I., additional

Published
2013
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48. Whole-Transcriptome Sequencing Identifies Novel IRF2BP2-CDX1 Fusion Gene Brought about by Translocation t(1;5)(q42;q32) in Mesenchymal Chondrosarcoma

Author

Nyquist, Kaja B., primary, Panagopoulos, Ioannis, additional, Thorsen, Jim, additional, Haugom, Lisbeth, additional, Gorunova, Ludmila, additional, Bjerkehagen, Bodil, additional, Fosså, Alexander, additional, Guriby, Marianne, additional, Nome, Torfinn, additional, Lothe, Ragnhild A., additional, Skotheim, Rolf I., additional, Heim, Sverre, additional, and Micci, Francesca, additional

Published
2012
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50. A novel transcript, VNN1-AB, as a biomarker for colorectal cancer.

Author

Løvf, Marthe, Nome, Torfinn, Bruun, Jarle, Eknæs, Mette, Bakken, Anne C., Mpindi, John P., Kilpinen, Sami, Rognum, Torleiv O., Nesbakken, Arild, Kallioniemi, Olli, Lothe, Ragnhild A., and Skotheim, Rolf I.

Abstract

Colorectal cancer is a global health challenge with high incidence rate and mortality. The patients' prognosis is strongly associated with disease stage and currently there is a need for improved prognostic and predictive biomarkers. In this study, novel colorectal cancer-specific transcript structures were nominated from whole transcriptome sequencing of seven colorectal cancer cell lines, two primary colorectal carcinomas with corresponding normal colonic mucosa and 16 normal tissues. The nominated transcripts were combined with gene level outlier expression analyses in a cohort of 505 colorectal cancers to identify biomarkers with capacity to stratify colorectal cancer subgroups. The transcriptome sequencing data and outlier expression analysis revealed 11 novel colorectal cancer-specific exon-exon junctions, of which 3 were located in the gene VNN1. The junctions within VNN1 were further characterized using rapid amplification of cDNA ends (RACE) and the prevalence of the subsequently characterized novel transcript, VNN1-AB, was investigated by real-time RT-PCR in 291 samples of miscellaneous origins. VNN1-AB was not present in any of the 43 normal colorectal tissue samples investigated, but in 5 of the 6 polyps, and 102 of the 136 (75%) colorectal cancers. We have identified a novel transcript of the VNN1 gene, with an organ-confined complete specificity for colorectal neoplasia. [ABSTRACT FROM AUTHOR]

Published
2014
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