Frequent TET2 mutations in systemic mastocytosis: Clinical, KITD816V and FIP1L1-PDGFRA correlates Journal Article
| Authors: | Tefferi, A.; Levine, R. L.; Lim, K. H.; Abdel-Wahab, O.; Lasho, T. L.; Patel, J.; Finke, C. M.; Mullally, A.; Li, C. Y.; Pardanani, A.; Gilliland, D. G. |
| Article Title: | Frequent TET2 mutations in systemic mastocytosis: Clinical, KITD816V and FIP1L1-PDGFRA correlates |
| Abstract: | TET2 (TET oncogene family member 2) is a candidate tumor suppressor gene located at chromosome 4q24, and was recently reported to be mutated in ∼14% of patients with JAK2V617F-positive myeloproliferative neoplasms. We used high-throughput DNA sequence analysis to screen for TET2 mutations in bone marrow-derived DNA from 48 patients with systemic mastocytosis (SM), including 42 who met the 2008 WHO (World Health Organization) diagnostic criteria for SM and 6 with FIP1L1-PDGFRA. Twelve (29%) SM, but no FIP1L1-PDGFRA patients, had TET2 mutations. A total of 17 mutations (13 frameshift, 2 nonsense and 2 missense) were documented in 2 (15%) of 13 indolent SM patients, 2 (40%) of 5 aggressive SM, and 8 (35%) of 23 SM associated with a clonal non-mast cell-lineage hematopoietic disease (P = 0.52). KITD816V was detected by PCR sequencing in 50 or 20% of patients with or without TET2 mutation (P = 0.05), respectively. Multivariable analysis showed a significant association between the presence of TET2 mutation and monocytosis (P = 0.0003) or female sex (P = 0.05). The association with monocytosis was also observed in non-indolent SM (n = 29), in which the presence of mutant TET2 did not affect survival (P = 0.98). We conclude that TET2 mutations are frequent in SM, segregate with KITD816V and influence phenotype without necessarily altering prognosis. |
| Keywords: | clinical article; controlled study; survival rate; unclassified drug; oncoprotein; sequence analysis; frameshift mutation; missense mutation; mutation; myeloproliferative disorder; dna-binding proteins; proto-oncogene proteins; janus kinase 2; pathogenesis; phenotype; platelet derived growth factor alpha receptor; proto-oncogene proteins c-kit; receptor, platelet-derived growth factor alpha; reverse transcription polymerase chain reaction; genetic association; high throughput screening; mutational analysis; cell lineage; hybrid protein; oncogene proteins, fusion; dna sequence; nonsense mutation; protein kitd; protein tet2; transcription factor fip1l1 platelet derived growth factor alpha receptor fusion protein; monocytosis; systemic mastocytosis; mastocytosis, systemic; mrna cleavage and polyadenylation factors |
| Journal Title: | Leukemia |
| Volume: | 23 |
| Issue: | 5 |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2009-05-01 |
| Start Page: | 900 |
| End Page: | 904 |
| Language: | English |
| DOI: | 10.1038/leu.2009.37 |
| PUBMED: | 19262599 |
| PROVIDER: | scopus |
| PMCID: | PMC4654631 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 36" - "Export Date: 30 November 2010" - "CODEN: LEUKE" - "Source: Scopus" |
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