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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
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.
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“genetic studies of MPN patients who subsequently transformed to AML identified TET2 mutations as a recurrent somatic mutation during progression from MPN to AML (Abdel-Wahab et al., 2010; Schaub et al., 2010).”
From Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation (2011) · cites this paper as Schaub et al., 2010
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Cited by
Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation
Moran-Crusio, K., Reavie, L., Shih, A., Abdel-Wahab, O., Ndiaye-Lobry, D., Lobry, C., Figueroa, M. E., Vasanthakumar, A., Patel, J., Zhao, X., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.06.001 · Cited by 1,339
Quivoron, C., Couronné, L., Della Valle, V., Lopez, C. K., Plo, I., Wagner-Ballon, O., Do Cruzeiro, M., Delhommeau, F., Arnulf, B., Stern, M.-H., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.06.003 · Cited by 924
Li, Z., Cai, X., Cai, C.-L., Wang, J., Zhang, W., Petersen, B. E., Yang, F.-C., & Xu, M. (2011) · Blood · doi:10.1182/blood-2010-12-325241 · Cited by 671
Ko, M., Bandukwala, H. S., An, J., Lamperti, E. D., Thompson, E. C., Hastie, R., Tsangaratou, A., Rajewsky, K., Koralov, S. B., & Rao, A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112317108 · Cited by 616
Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans
Kaasinen, E., Kuismin, O., Rajamäki, K., Ristolainen, H., Aavikko, M., Kondelin, J., Saarinen, S., Berta, D. G., Katainen, R., Hirvonen, E. A. M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09198-7 · Cited by 92
Self-citation
Metadata
- Authors
- Schaub, F. X., Looser, R., Li, S., Hao-Shen, H., Lehmann, T., Tichelli, A., & Skoda, R. C.
- Affiliations
- Department of Biomedicine, Experimental Hematology,
- Department of Hematology, and
- Division of Diagnostic Hematology, University Hospital Basel, Basel, Switzerland
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2010-03-11
- Volume
- 115
- Issue
- 10
- Pages
- 2003-2007
- ISSN
- 0006-4971
- 1528-0020
- Cited by
- 157
- References
- 2
- Language
- en
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