Somatic MED12 mutations are associated with poor prognosis markers in chronic lymphocytic leukemia

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http://hdl.handle.net/10138/225310

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Kampjarvi , K , Jaervinen , T M , Heikkinen , T , Ruppert , A S , Senter , L , Hoag , K W , Dufva , O , Kontro , M , Rassenti , L , Hertlein , E , Kipps , T J , Porkka , K , Byrd , J C , de la Chapelle , A & Vahteristo , P 2015 , ' Somatic MED12 mutations are associated with poor prognosis markers in chronic lymphocytic leukemia ' , Oncotarget , vol. 6 , no. 3 , pp. 1884-1888 . https://doi.org/10.18632/oncotarget.2753

Title: Somatic MED12 mutations are associated with poor prognosis markers in chronic lymphocytic leukemia
Author: Kampjarvi, Kati; Jaervinen, Tiina M.; Heikkinen, Tuomas; Ruppert, Amy S.; Senter, Leigha; Hoag, Kevin W.; Dufva, Olli; Kontro, Mika; Rassenti, Laura; Hertlein, Erin; Kipps, Thomas J.; Porkka, Kimmo; Byrd, John C.; de la Chapelle, Albert; Vahteristo, Pia
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Department of Medicine
University of Helsinki, Clinicum
University of Helsinki, Research Programs Unit
Date: 2015-01-30
Language: eng
Number of pages: 5
Belongs to series: Oncotarget
ISSN: 1949-2553
URI: http://hdl.handle.net/10138/225310
Abstract: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. We performed systematic database search and identified highly specific MED12 mutations in CLL patients. To study this further, we collected three independent sample series comprising over 700 CLL samples and screened MED12 exons 1 and 2 by direct sequencing. Mutations were identified at significant frequency in all three series with a combined mutation frequency of 5.2% (37/709). Positive mutation status was found to be associated with unmutated IGHV and ZAP70 expression, which are well-known poor prognosis markers in CLL. Our results recognize CLL as the first extrauterine cancer type where 5'terminus of MED12 is mutated at significant frequency. Functional analyses have shown that these mutations lead to dissociation of Cyclin C-CDK8/19 from the core Mediator and to the loss of Mediator-associated CDK kinase activity. Additional studies on the role of MED12 mutation status as a putative prognostic factor as well as mutations' exact tumorigenic mechanism in CLL are warranted.
Subject: Chronic lymphocytic leukemia
MED12
somatic mutation
cancer genetics
prognosis
UTERINE LEIOMYOMAS
ZAP-70 EXPRESSION
GENE
CANCER
PROGRESSION
EVOLUTION
SF3B1
3122 Cancers
3111 Biomedicine
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