Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies Journal Article
| Authors: | Abdel-Wahab, O.; Mullally, A.; Hedvat, C.; Garcia-Manero, G.; Patel, J.; Wadleigh, M.; Malinge, S.; Yao, J.; Kilpivaara, O.; Bhat, R.; Huberman, K.; Thomas, S.; Dolgalev, I.; Heguy, A.; Paietta, E.; Le Beau, M. M.; Beran, M.; Tallman, M. S.; Ebert, B. L.; Kantarjian, H. M.; Stone, R. M.; Gilliland, D. G.; Crispino, J. D.; Levine, R. L. |
| Article Title: | Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies |
| Abstract: | Disease alleles that activate signal transduction are common in myeloid malignancies; however, there are additional unidentified mutations that contribute to myeloid transformation. Based on the recent identification of TET2 mutations, we evaluated the mutational status of TET1, TET2, and TET3 in myeloproliferative neoplasms (MPNs), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). Sequencing of TET2 in 408 paired tumor/normal samples distinguished between 68 somatic mutations and 6 novel single nucleotide polymorphisms and identified TET2 mutations in MPN (27 of 354, 7.6%), CMML (29 of 69, 42%), AML (11 of 91, 12%), and M7 AML (1 of 28, 3.6%) samples.We did not identify somatic TET1 or TET3 mutations or TET2 promoter hypermethylation in MPNs. TET2 mutations did not cluster in genetically defined MPN, CMML, or AML subsets but were associated with decreased overall survival in AML (P = .029). These data indicate that TET2 mutations are observed in different myeloid malignancies and may be important in AML prognosis. © 2009 by The American Society of Hematology. |
| Keywords: | cancer survival; myeloproliferative disorders; survival rate; carrier protein; ten eleven translocation 1; ten eleven translocation 2; ten eleven translocation 3; unclassified drug; dna binding protein; oncoprotein; tet1 protein, human; tet2 protein, human; acute granulocytic leukemia; chronic myelomonocytic leukemia; gene cluster; gene mutation; gene sequence; gene translocation; genetic trait; human cell; major clinical study; methylation; overall survival; promoter region; sequence analysis; single nucleotide polymorphism; somatic mutation; case control study; exon; frameshift mutation; gene deletion; genetics; missense mutation; mutation; myeloproliferative disorder; stop codon; case-control studies; codon, nonsense; dna-binding proteins; exons; leukemia, myeloid, acute; leukemia, myelomonocytic, chronic; mutation, missense; polymorphism, single nucleotide; proto-oncogene proteins; sequence deletion |
| Journal Title: | Blood |
| Volume: | 114 |
| Issue: | 1 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2009-07-02 |
| Start Page: | 144 |
| End Page: | 147 |
| Language: | English |
| DOI: | 10.1182/blood-2009-03-210039 |
| PUBMED: | 19420352 |
| PROVIDER: | scopus |
| PMCID: | PMC2710942 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 39" - "Export Date: 30 November 2010" - "CODEN: BLOOA" - "Source: Scopus" |
Altmetric Score
MSK Authors
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85Heguy -
123Hedvat -
24Yao -
490Levine -
11Kilpivaara -
24Huberman -
11Dolgalev -
348Abdel-Wahab -
53
Patel -
3
Thomas
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