Recurrent CDKN1B (p27) mutations in hairy cell leukemia Journal Article
| Authors: | Dietrich, S.; Hüllein, J.; Lee, S. C. W.; Hutter, B.; Gonzalez, D.; Jayne, S.; Dyer, M. J. S.; Oleś, M.; Else, M.; Liu, X.; Słabicki, M.; Wu, B.; Troussard, X.; Dürig, J.; Andrulis, M.; Dearden, C.; Von Kalle, C.; Granzow, M.; Jauch, A.; Fröhling, S.; Huber, W.; Meggendorfer, M.; Haferlach, T.; Ho, A. D.; Richter, D.; Brors, B.; Glimm, H.; Matutes, E.; Wahab, O. A.; Zenz, T. |
| Article Title: | Recurrent CDKN1B (p27) mutations in hairy cell leukemia |
| Abstract: | Hairy cell leukemia (HCL) is marked by near 100% mutational frequency of BRAFV600E mutations. Recurrent cooperating genetic events that may contribute to HCL pathogenesis or affect the clinical course of HCL are currently not described. Therefore, we performed whole exome sequencing to explore the mutational landscape of purine analog refractory HCL. In addition to the disease-defining BRAFV600E mutations, we identified mutations in EZH2, ARID1A, and recurrent inactivating mutations of the cell cycle inhibitor CDKN1B (p27). Targeted deep sequencing of CDKN1B in a larger cohort of HCL patients identify deleterious CDKN1B mutations in 16% of patients with HCL (n = 13 of 81). In 11 of 13 patients the CDKN1B mutation was clonal, implying an early role of CDKN1B mutations in the pathogenesis of HCL. CDKN1B mutations were not found to impact clinical characteristics or outcome in this cohort. These data identify HCL as having the highest frequency of CDKN1B mutations among cancers and identify CDNK1B as the second most common mutated gene in HCL. Moreover, given the known function of CDNK1B, these data suggest a novel role for alterations in regulation of cell cycle and senescence in HCL with CDKN1B mutations. © 2015 by The American Society of Hematology. |
| Keywords: | gene mutation; gene sequence; major clinical study; sequence analysis; pathogenesis; outcome assessment; cyclin dependent kinase inhibitor 1b; histone h3; recurrent disease; purine derivative; senescence; cyclin dependent kinase inhibitor 1a; cyclin dependent kinase inhibitor 2a; cell cycle regulation; b raf kinase; cyclin e; cyclin dependent kinase 4; leukemia remission; genetic identification; cyclin d; hairy cell leukemia; copy number variation; cyclin dependent kinase 2; transcription factor ezh2; histone demethylase; vemurafenib; retinoblastoma binding protein 2; exome; calcium calmodulin dependent protein kinase; human; priority journal; article; whole exome sequencing |
| Journal Title: | Blood |
| Volume: | 126 |
| Issue: | 8 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2015-08-20 |
| Start Page: | 1005 |
| End Page: | 1008 |
| Language: | English |
| DOI: | 10.1182/blood-2015-04-643361 |
| PROVIDER: | scopus |
| PUBMED: | 26065650 |
| DOI/URL: | |
| Notes: | Export Date: 2 October 2015 -- Source: Scopus |
