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Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms

Schaub, Franz X. and Looser, Renate and Li, Sai and Hao-Shen, Hui and Lehmann, Thomas and Tichelli, Andre and Skoda, Radek C.. (2010) Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms. Blood, Vol. 115, H. 10. pp. 2003-2007.

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Official URL: http://edoc.unibas.ch/dok/A6006831

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Abstract

Somatic mutations in TET2 occur in patients with myeloproliferative neoplasms and other hematologic malignancies. It has been suggested that TET2 is a tumor suppressor gene and mutations in TET2 precede the acquisition of JAK2-V617F. To examine the order of events, we performed colony assays and genotyped TET2 and JAK2 in individual colonies. In 4 of 8 myeloproliferative neoplasm patients, we found that some colonies with mutated TET2 carried wild-type JAK2, whereas others were JAK2-V617F positive, indicating that TET2 occurred before JAK2-V617F. One of these patients carried a germline TET2 mutation. However, in 2 other patients, we obtained data compatible with the opposite order of events, with JAK2 exon 12 mutation preceding TET2 mutation in one case. Finally, in 2 of 8 patients, the TET2 and JAK2-V617F mutations defined 2 separate clones. The lack of a strict temporal order of occurrence makes it unlikely that mutations in TET2 represent a predisposing event for acquiring mutations in JAK2.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Ehemalige Einheiten Querschnittsfächer (Klinik) > Diagnostische Hämatologie (Tichelli)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Ehemalige Einheiten Querschnittsfächer (Klinik) > Diagnostische Hämatologie (Tichelli)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Hämatologie > Molekulare Medizin (Skoda)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Hämatologie > Molekulare Medizin (Skoda)
UniBasel Contributors:Skoda, Radek C. and Tichelli, André
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society of Hematology
ISSN:1528-0020
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:21 Jun 2013 12:29
Deposited On:21 Jun 2013 12:24

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