TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis Journal Article

   

Authors:	Tefferi, A.; Pardanani, A.; Lim, K. H.; Abdel-Wahab, O.; Lasho, T. L.; Patel, J.; Gangat, N.; Finke, C. M.; Schwager, S.; Mullally, A.; Li, C. Y.; Hanson, C. A.; Mesa, R.; Bernard, O.; Delhommeau, F.; Vainchenker, W.; Gilliland, D. G.; Levine, R. L.
Article Title:	TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis
Abstract:	High-throughput DNA sequence analysis was used to screen for TET2 mutations in bone marrow-derived DNA from 239 patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). Thirty-two mutations (19 frameshift, 10 nonsense, 3 missense; mostly involving exons 4 and 12) were identified for an overall mutational frequency of ∼13%. Specific diagnoses included polycythemia vera (PV; n = 89), essential thrombocythemia (ET; n = 57), primary myelofibrosis (PMF; n = 60), post-PV MF (n = 14), post-ET MF (n = 7) and blast phase PV/ET/MF (n = 12); the corresponding mutational frequencies were ∼16, 5, 17, 14, 14 and 17% (P=0.50). Mutant TET2 was detected in ∼17 and ∼7% of JAK2V617F-positive and -negative cases, respectively (P=0.04). However, this apparent clustering of the two mutations was accounted for by an independent association between mutant TET2 and advanced age; mutational frequency was ∼23% in patients ≥60 years old versus ∼4% in younger patients (P < 0.0001). The presence of mutant TET2 did not affect survival, leukemic transformation or thrombosis in either PV or PMF; a correlation with hemoglobin <10 g per 100ml in PMF was noted (P = 0.05). We conclude that TET2 mutations occur in both JAK2V617F-positive and -negative MPN, are more prevalent in older patients, display similar frequencies across MPN subcategories and disease stages, and hold limited prognostic relevance.
Keywords:	adult; aged; aged, 80 and over; middle aged; myelofibrosis; survival rate; unclassified drug; gene cluster; gene mutation; major clinical study; exon; frameshift mutation; missense mutation; mutation; dna-binding proteins; proto-oncogene proteins; janus kinase 2; primary myelofibrosis; genetic association; gene frequency; gene product; high throughput screening; mutational analysis; gene identification; nucleotide sequence; leukemogenesis; age distribution; thrombotic thrombocytopenic purpura; protein jak2v617f; nonsense mutation; polycythemia vera; protein tet2; genetic correlation; thrombocythemia, essential
Journal Title:	Leukemia
Volume:	23
Issue:	5
ISSN:	0887-6924
Publisher:	Nature Publishing Group
Date Published:	2009-05-01
Start Page:	905
End Page:	911
Language:	English
DOI:	10.1038/leu.2009.47
PUBMED:	19262601
PROVIDER:	scopus
PMCID:	PMC4654629
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-67349124376&partnerID=40&md5=f9c0a90a1fe7f56d38f7297b95fd8124
Notes:	--- - "Cited By (since 1996): 59" - "Export Date: 30 November 2010" - "CODEN: LEUKE" - "Source: Scopus"

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