Distinct expression profile in fumarate-hydratase-deficient uterine fibroids

Sakari Vanharanta, Patrick J Pollard, Heli J Lehtonen, Päivi Laiho, Jari Sjöberg, Arto Leminen, Kristiina Aittomäki, Johanna Arola, Mogens Kruhøffer, Torben F Ørntoft, Ian P Tomlinson, Maija Kiuru, Diego Arango, Lauri A Aaltonen

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    "Defects in mitochondrial enzymes predispose to severe developmental defects as well as tumorigenesis. Heterozygous germline mutations in the nuclear gene encoding fumarate hydratase (FH), an enzyme catalyzing the hydration of fumarate in the Krebs tricarboxylic acid cycle, cause hereditary leiomyomatosis and renal cell cancer; yet the connection between disruption of mitochondrial metabolic pathways and neoplasia remains to be discovered. We have used an expression microarray approach for studying differences in global gene expression pattern caused by mutations in FH. Seven uterine fibroids carrying FH mutations were compared with 15 fibroids with wild-type FH. The two groups showed markedly different expression profiles, and multiple differentially expressed genes were detected. The most significant increase in FH mutants was seen in the expression of carbohydrate metabolism- and glycolysis-related genes. Other significantly up-regulated gene categories in FH mutants were, for example, iron ion homeostasis and oxidoreduction. Genes with lower expression in FH-mutant fibroids belonged to groups such as extracellular matrix, cell adhesion, muscle development and cell contraction. We show that FH mutations alter significantly the expression profiles of fibroids, most strikingly increasing the expression of genes involved in glycolysis."
    Original languageEnglish
    JournalHuman Molecular Genetics
    Volume15
    Issue number1
    Pages (from-to)97-103
    Number of pages7
    ISSN0964-6906
    DOIs
    Publication statusPublished - 2006
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine

    Cite this

    Vanharanta, Sakari ; Pollard, Patrick J ; Lehtonen, Heli J ; Laiho, Päivi ; Sjöberg, Jari ; Leminen, Arto ; Aittomäki, Kristiina ; Arola, Johanna ; Kruhøffer, Mogens ; Ørntoft, Torben F ; Tomlinson, Ian P ; Kiuru, Maija ; Arango, Diego ; Aaltonen, Lauri A. / Distinct expression profile in fumarate-hydratase-deficient uterine fibroids. In: Human Molecular Genetics. 2006 ; Vol. 15, No. 1. pp. 97-103.
    @article{c712f0af930941b29723fcc6baab8c7f,
    title = "Distinct expression profile in fumarate-hydratase-deficient uterine fibroids",
    abstract = "{"}Defects in mitochondrial enzymes predispose to severe developmental defects as well as tumorigenesis. Heterozygous germline mutations in the nuclear gene encoding fumarate hydratase (FH), an enzyme catalyzing the hydration of fumarate in the Krebs tricarboxylic acid cycle, cause hereditary leiomyomatosis and renal cell cancer; yet the connection between disruption of mitochondrial metabolic pathways and neoplasia remains to be discovered. We have used an expression microarray approach for studying differences in global gene expression pattern caused by mutations in FH. Seven uterine fibroids carrying FH mutations were compared with 15 fibroids with wild-type FH. The two groups showed markedly different expression profiles, and multiple differentially expressed genes were detected. The most significant increase in FH mutants was seen in the expression of carbohydrate metabolism- and glycolysis-related genes. Other significantly up-regulated gene categories in FH mutants were, for example, iron ion homeostasis and oxidoreduction. Genes with lower expression in FH-mutant fibroids belonged to groups such as extracellular matrix, cell adhesion, muscle development and cell contraction. We show that FH mutations alter significantly the expression profiles of fibroids, most strikingly increasing the expression of genes involved in glycolysis.{"}",
    keywords = "311 Basic medicine",
    author = "Sakari Vanharanta and Pollard, {Patrick J} and Lehtonen, {Heli J} and P{\"a}ivi Laiho and Jari Sj{\"o}berg and Arto Leminen and Kristiina Aittom{\"a}ki and Johanna Arola and Mogens Kruh{\o}ffer and {\O}rntoft, {Torben F} and Tomlinson, {Ian P} and Maija Kiuru and Diego Arango and Aaltonen, {Lauri A}",
    year = "2006",
    doi = "10.1093/hmg/ddi431",
    language = "English",
    volume = "15",
    pages = "97--103",
    journal = "Human Molecular Genetics",
    issn = "0964-6906",
    publisher = "Oxford University Press",
    number = "1",

    }

    Vanharanta, S, Pollard, PJ, Lehtonen, HJ, Laiho, P, Sjöberg, J, Leminen, A, Aittomäki, K, Arola, J, Kruhøffer, M, Ørntoft, TF, Tomlinson, IP, Kiuru, M, Arango, D & Aaltonen, LA 2006, 'Distinct expression profile in fumarate-hydratase-deficient uterine fibroids', Human Molecular Genetics, vol. 15, no. 1, pp. 97-103. https://doi.org/10.1093/hmg/ddi431

    Distinct expression profile in fumarate-hydratase-deficient uterine fibroids. / Vanharanta, Sakari; Pollard, Patrick J; Lehtonen, Heli J; Laiho, Päivi; Sjöberg, Jari; Leminen, Arto; Aittomäki, Kristiina; Arola, Johanna; Kruhøffer, Mogens; Ørntoft, Torben F; Tomlinson, Ian P; Kiuru, Maija; Arango, Diego; Aaltonen, Lauri A.

    In: Human Molecular Genetics, Vol. 15, No. 1, 2006, p. 97-103.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - Distinct expression profile in fumarate-hydratase-deficient uterine fibroids

    AU - Vanharanta, Sakari

    AU - Pollard, Patrick J

    AU - Lehtonen, Heli J

    AU - Laiho, Päivi

    AU - Sjöberg, Jari

    AU - Leminen, Arto

    AU - Aittomäki, Kristiina

    AU - Arola, Johanna

    AU - Kruhøffer, Mogens

    AU - Ørntoft, Torben F

    AU - Tomlinson, Ian P

    AU - Kiuru, Maija

    AU - Arango, Diego

    AU - Aaltonen, Lauri A

    PY - 2006

    Y1 - 2006

    N2 - "Defects in mitochondrial enzymes predispose to severe developmental defects as well as tumorigenesis. Heterozygous germline mutations in the nuclear gene encoding fumarate hydratase (FH), an enzyme catalyzing the hydration of fumarate in the Krebs tricarboxylic acid cycle, cause hereditary leiomyomatosis and renal cell cancer; yet the connection between disruption of mitochondrial metabolic pathways and neoplasia remains to be discovered. We have used an expression microarray approach for studying differences in global gene expression pattern caused by mutations in FH. Seven uterine fibroids carrying FH mutations were compared with 15 fibroids with wild-type FH. The two groups showed markedly different expression profiles, and multiple differentially expressed genes were detected. The most significant increase in FH mutants was seen in the expression of carbohydrate metabolism- and glycolysis-related genes. Other significantly up-regulated gene categories in FH mutants were, for example, iron ion homeostasis and oxidoreduction. Genes with lower expression in FH-mutant fibroids belonged to groups such as extracellular matrix, cell adhesion, muscle development and cell contraction. We show that FH mutations alter significantly the expression profiles of fibroids, most strikingly increasing the expression of genes involved in glycolysis."

    AB - "Defects in mitochondrial enzymes predispose to severe developmental defects as well as tumorigenesis. Heterozygous germline mutations in the nuclear gene encoding fumarate hydratase (FH), an enzyme catalyzing the hydration of fumarate in the Krebs tricarboxylic acid cycle, cause hereditary leiomyomatosis and renal cell cancer; yet the connection between disruption of mitochondrial metabolic pathways and neoplasia remains to be discovered. We have used an expression microarray approach for studying differences in global gene expression pattern caused by mutations in FH. Seven uterine fibroids carrying FH mutations were compared with 15 fibroids with wild-type FH. The two groups showed markedly different expression profiles, and multiple differentially expressed genes were detected. The most significant increase in FH mutants was seen in the expression of carbohydrate metabolism- and glycolysis-related genes. Other significantly up-regulated gene categories in FH mutants were, for example, iron ion homeostasis and oxidoreduction. Genes with lower expression in FH-mutant fibroids belonged to groups such as extracellular matrix, cell adhesion, muscle development and cell contraction. We show that FH mutations alter significantly the expression profiles of fibroids, most strikingly increasing the expression of genes involved in glycolysis."

    KW - 311 Basic medicine

    U2 - 10.1093/hmg/ddi431

    DO - 10.1093/hmg/ddi431

    M3 - Article

    VL - 15

    SP - 97

    EP - 103

    JO - Human Molecular Genetics

    JF - Human Molecular Genetics

    SN - 0964-6906

    IS - 1

    ER -