Characterization of MED12, HMGA2, and FH alterations reveals molecular variability in uterine smooth muscle tumors

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Makinen , N , Kampjarvi , K , Frizzell , N , Butzow , R & Vahteristo , P 2017 , ' Characterization of MED12, HMGA2, and FH alterations reveals molecular variability in uterine smooth muscle tumors ' , Molecular Cancer , vol. 16 , 101 . https://doi.org/10.1186/s12943-017-0672-1

Title: Characterization of MED12, HMGA2, and FH alterations reveals molecular variability in uterine smooth muscle tumors
Author: Makinen, Netta; Kampjarvi, Kati; Frizzell, Norma; Butzow, Ralf; Vahteristo, Pia
Other contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, HUSLAB
University of Helsinki, Research Programs Unit







Date: 2017-06-07
Language: eng
Number of pages: 8
Belongs to series: Molecular Cancer
ISSN: 1476-4598
DOI: https://doi.org/10.1186/s12943-017-0672-1
URI: http://hdl.handle.net/10138/197733
Abstract: Uterine smooth muscle tumors range from benign leiomyomas to malignant leiomyosarcomas. Based on numerous molecular studies, leiomyomas and leiomyosarcomas mostly lack shared mutations and the majority of tumors are believed to develop through distinct mechanisms. To further characterize the molecular variability among uterine smooth muscle tumors, and simultaneously insinuate their potential malignant progression, we examined the frequency of known genetic leiomyoma driver alterations (MED12 mutations, HMGA2 overexpression, biallelic FH inactivation) in 65 conventional leiomyomas, 94 histopathological leiomyoma variants (18 leiomyomas with bizarre nuclei, 22 cellular, 29 highly cellular, and 25 mitotically active leiomyomas), and 51 leiomyosarcomas. Of the 210 tumors analyzed, 107 had mutations in one of the three driver genes. No tumor had more than one mutation confirming that all alterations are mutually exclusive. MED12 mutations were the most common alterations in conventional and mitotically active leiomyomas and leiomyosarcomas, while leiomyomas with bizarre nuclei were most often FH deficient and cellular tumors showed frequent HMGA2 overexpression. Highly cellular leiomyomas displayed the least amount of alterations leaving the majority of tumors with no known driver aberration. Our results indicate that based on the molecular background, histopathological leiomyoma subtypes do not only differ from conventional leiomyomas, but also from each other. The presence of leiomyoma driver alterations in nearly one third of leiomyosarcomas suggests that some tumors arise through leiomyoma precursor lesion or that these mutations provide growth advantage also to highly aggressive cancers. It is clinically relevant to understand the molecular background of various smooth muscle tumor subtypes, as it may lead to improved diagnosis and personalized treatments in the future.
Subject: Uterine leiomyoma
Histopathological uterine leiomyoma variants
Uterine leiomyosarcoma
MED12
HMGA2
FH
RENAL-CELL CANCER
MITOTICALLY ACTIVE LEIOMYOMAS
HEREDITARY LEIOMYOMATOSIS
SYMPLASTIC LEIOMYOMA
UTERUS
MUTATIONS
LEIOMYOSARCOMA
INACTIVATION
FEATURES
TISSUE
3122 Cancers
3111 Biomedicine
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