Novel TET2 mutations associated with UPD4q24 in myelodysplastic syndrome - PubMed (original) (raw)
. 2009 Aug 20;27(24):4002-6.
doi: 10.1200/JCO.2009.22.6985. Epub 2009 Jun 15.
Affiliations
- PMID: 19528370
- DOI: 10.1200/JCO.2009.22.6985
Novel TET2 mutations associated with UPD4q24 in myelodysplastic syndrome
Azim M Mohamedali et al. J Clin Oncol. 2009.
Abstract
Purpose: Cryptic chromosomal aberrations, such as regions of uniparental disomy (UPD), have been shown to harbor homozygous mutations and are a common feature in myelodysplastic syndrome (MDS). We investigated the sequence integrity of 4q24 candidate tumor suppressor gene TET2 in MDS patients with UPD on chromosome 4.
Patients and methods: The coding exons of TET2 were analyzed by 454 deep sequencing and Sanger sequencing in nine patients with UPD on 4q. Four patients had refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS) and UPD4q24, and five patients (refractory anemia with excess blasts-II, n = 1; 5q- syndrome, n = 1; RCMD-RS, n = 1; refractory anemia, n = 1; refractory cytopenia with multilineage dysplasia, n = 1) had no UPD4q24.
Results: Mutations on TET2 were identified in all four patients with UPD4q24. These were localized to exons 3, 6, and 9 and resulted in two premature stop codons, one frameshift mutation, and one cysteine to glycine amino acid change. Mutant clone size varied between 30% and 85%. One patient with UPD outside of q24 (UPD4q28.3) displayed additional TET2 mutations, but these were at low clonal levels (13%, 4%, and 4% for a silent mutation, a 180-base pair deletion in exon 3, and a lysine to phenylalanine substitution in exon 11, respectively). The other patients who did not have UPD4q24 did not have verifiable TET2 mutations.
Conclusion: Our data identify novel TET2 mutations in a dominant clone in patients with UPD4q24. The presence of UPD4q24 and mutations in RCMD-RS patients may suggest specificity to this subtype. Our preliminary results need to be confirmed in a large cohort of all MDS subtypes.
Similar articles
- Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes.
Mohamedali A, Gäken J, Twine NA, Ingram W, Westwood N, Lea NC, Hayden J, Donaldson N, Aul C, Gattermann N, Giagounidis A, Germing U, List AF, Mufti GJ. Mohamedali A, et al. Blood. 2007 Nov 1;110(9):3365-73. doi: 10.1182/blood-2007-03-079673. Epub 2007 Jul 18. Blood. 2007. PMID: 17634407 - Mutation in TET2 in myeloid cancers.
Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Massé A, Kosmider O, Le Couedic JP, Robert F, Alberdi A, Lécluse Y, Plo I, Dreyfus FJ, Marzac C, Casadevall N, Lacombe C, Romana SP, Dessen P, Soulier J, Viguié F, Fontenay M, Vainchenker W, Bernard OA. Delhommeau F, et al. N Engl J Med. 2009 May 28;360(22):2289-301. doi: 10.1056/NEJMoa0810069. N Engl J Med. 2009. PMID: 19474426 - Case report: A novel TET2 mutation in a patient with refractory cytopenia with multilineage dysplasia.
Coutinho DF, Diniz C, Filgueiras RL, Baptista RL, Ayres-Silva JP, Monte-Mór BC, Bonamino MH, Zalcberg IR. Coutinho DF, et al. Genet Mol Res. 2013 Nov 22;12(4):5858-62. doi: 10.4238/2013.November.22.13. Genet Mol Res. 2013. PMID: 24301955 - [Mutation of tet2 gene and malignant blood disease].
Qian XF, Shen YF, Zhang SJ, Li JY. Qian XF, et al. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Aug;18(4):1096-100. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010. PMID: 20723337 Review. Chinese. - Mutations of the TET2 and CBL genes: novel molecular markers in myeloid malignancies.
Bacher U, Haferlach C, Schnittger S, Kohlmann A, Kern W, Haferlach T. Bacher U, et al. Ann Hematol. 2010 Jul;89(7):643-52. doi: 10.1007/s00277-010-0920-6. Epub 2010 Mar 2. Ann Hematol. 2010. PMID: 20195608 Review.
Cited by
- The emerging insights into catalytic or non-catalytic roles of TET proteins in tumors and neural development.
Lian H, Li WB, Jin WL. Lian H, et al. Oncotarget. 2016 Sep 27;7(39):64512-64525. doi: 10.18632/oncotarget.11412. Oncotarget. 2016. PMID: 27557497 Free PMC article. Review. - Prognosis of Primary Myelofibrosis in the Genomic Era.
Bose P, Verstovsek S. Bose P, et al. Clin Lymphoma Myeloma Leuk. 2016 Aug;16 Suppl:S105-13. doi: 10.1016/j.clml.2016.02.031. Clin Lymphoma Myeloma Leuk. 2016. PMID: 27521306 Free PMC article. Review. - Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance.
Grimwade D, Ivey A, Huntly BJ. Grimwade D, et al. Blood. 2016 Jan 7;127(1):29-41. doi: 10.1182/blood-2015-07-604496. Epub 2015 Dec 10. Blood. 2016. PMID: 26660431 Free PMC article. Review. - Genetic Characterization of Ten-Eleven-Translocation Methylcytosine Dioxygenase Alterations in Human Glioma.
Kraus TF, Greiner A, Steinmaurer M, Dietinger V, Guibourt V, Kretzschmar HA. Kraus TF, et al. J Cancer. 2015 Jul 15;6(9):832-42. doi: 10.7150/jca.12010. eCollection 2015. J Cancer. 2015. PMID: 26284134 Free PMC article. - Prognostic relevance of acquired uniparental disomy in serous ovarian cancer.
Tuna M, Ju Z, Smid M, Amos CI, Mills GB. Tuna M, et al. Mol Cancer. 2015 Feb 3;14(1):29. doi: 10.1186/s12943-015-0289-1. Mol Cancer. 2015. PMID: 25644622 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous