Tags

Type your tag names separated by a space and hit enter

Biallelic inactivation of fumarate hydratase (FH) occurs in nonsyndromic uterine leiomyomas but is rare in other tumors.
Am J Pathol. 2004 Jan; 164(1):17-22.AJ

Abstract

Germline mutations in the fumarate hydratase (FH) gene at 1q43 predispose to dominantly inherited cutaneous and uterine leiomyomas, uterine leiomyosarcoma, and papillary renal cell cancer (HLRCC syndrome). To evaluate the role of FH inactivation in sporadic tumorigenesis, we analyzed a series of 299 malignant tumors representing 10 different malignant tumor types for FH mutations. Additionally, 153 uterine leiomyomas from 46 unselected individuals were subjected to and informative in loss of heterozygosity analysis at the FH locus, and the five (3.3%) tumors displaying loss of heterozygosity were subjected to FH mutation analysis. Although mutation search in the 299 malignant tumors was negative, somatic FH mutations were found in two nonsyndromic leiomyomas; a splice site change IVS4 + 3A>G, leading to deletion of exon four, and a missense mutation Ala196Thr. The occurrence of somatic mutations strongly suggests that FH is a true target of the 1q43 deletions. Although uterine leiomyomas are the most common tumors of women, specific inactivating somatic mutations contributing to the formation of nonsyndromic leiomyomas have not been reported previously. Taking into account the apparent risk of uterine leiomyosarcoma associated with FH germline mutations, the finding raises the possibility that also some nonsyndromic leiomyomas may have a genetic profile that is more prone to malignant degeneration. Our data also indicate that somatic FH mutations appear to be limited to tumor types observed in hereditary leiomyomatosis and renal cell cancer.

Authors+Show Affiliations

Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14695314

Citation

Lehtonen, Rainer, et al. "Biallelic Inactivation of Fumarate Hydratase (FH) Occurs in Nonsyndromic Uterine Leiomyomas but Is Rare in Other Tumors." The American Journal of Pathology, vol. 164, no. 1, 2004, pp. 17-22.
Lehtonen R, Kiuru M, Vanharanta S, et al. Biallelic inactivation of fumarate hydratase (FH) occurs in nonsyndromic uterine leiomyomas but is rare in other tumors. Am J Pathol. 2004;164(1):17-22.
Lehtonen, R., Kiuru, M., Vanharanta, S., Sjöberg, J., Aaltonen, L. M., Aittomäki, K., Arola, J., Butzow, R., Eng, C., Husgafvel-Pursiainen, K., Isola, J., Järvinen, H., Koivisto, P., Mecklin, J. P., Peltomäki, P., Salovaara, R., Wasenius, V. M., Karhu, A., Launonen, V., ... Aaltonen, L. A. (2004). Biallelic inactivation of fumarate hydratase (FH) occurs in nonsyndromic uterine leiomyomas but is rare in other tumors. The American Journal of Pathology, 164(1), 17-22.
Lehtonen R, et al. Biallelic Inactivation of Fumarate Hydratase (FH) Occurs in Nonsyndromic Uterine Leiomyomas but Is Rare in Other Tumors. Am J Pathol. 2004;164(1):17-22. PubMed PMID: 14695314.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biallelic inactivation of fumarate hydratase (FH) occurs in nonsyndromic uterine leiomyomas but is rare in other tumors. AU - Lehtonen,Rainer, AU - Kiuru,Maija, AU - Vanharanta,Sakari, AU - Sjöberg,Jari, AU - Aaltonen,Leena-Maija, AU - Aittomäki,Kristiina, AU - Arola,Johanna, AU - Butzow,Ralf, AU - Eng,Charis, AU - Husgafvel-Pursiainen,Kirsti, AU - Isola,Jorma, AU - Järvinen,Heikki, AU - Koivisto,Pasi, AU - Mecklin,Jukka-Pekka, AU - Peltomäki,Päivi, AU - Salovaara,Reijo, AU - Wasenius,Veli-Matti, AU - Karhu,Auli, AU - Launonen,Virpi, AU - Nupponen,Nina N, AU - Aaltonen,Lauri A, PY - 2003/12/26/pubmed PY - 2004/2/28/medline PY - 2003/12/26/entrez SP - 17 EP - 22 JF - The American journal of pathology JO - Am. J. Pathol. VL - 164 IS - 1 N2 - Germline mutations in the fumarate hydratase (FH) gene at 1q43 predispose to dominantly inherited cutaneous and uterine leiomyomas, uterine leiomyosarcoma, and papillary renal cell cancer (HLRCC syndrome). To evaluate the role of FH inactivation in sporadic tumorigenesis, we analyzed a series of 299 malignant tumors representing 10 different malignant tumor types for FH mutations. Additionally, 153 uterine leiomyomas from 46 unselected individuals were subjected to and informative in loss of heterozygosity analysis at the FH locus, and the five (3.3%) tumors displaying loss of heterozygosity were subjected to FH mutation analysis. Although mutation search in the 299 malignant tumors was negative, somatic FH mutations were found in two nonsyndromic leiomyomas; a splice site change IVS4 + 3A>G, leading to deletion of exon four, and a missense mutation Ala196Thr. The occurrence of somatic mutations strongly suggests that FH is a true target of the 1q43 deletions. Although uterine leiomyomas are the most common tumors of women, specific inactivating somatic mutations contributing to the formation of nonsyndromic leiomyomas have not been reported previously. Taking into account the apparent risk of uterine leiomyosarcoma associated with FH germline mutations, the finding raises the possibility that also some nonsyndromic leiomyomas may have a genetic profile that is more prone to malignant degeneration. Our data also indicate that somatic FH mutations appear to be limited to tumor types observed in hereditary leiomyomatosis and renal cell cancer. SN - 0002-9440 UR - https://www.unboundmedicine.com/medline/citation/14695314/Biallelic_inactivation_of_fumarate_hydratase__FH__occurs_in_nonsyndromic_uterine_leiomyomas_but_is_rare_in_other_tumors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(10)63091-X DB - PRIME DP - Unbound Medicine ER -