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.

journal_name

Blood

journal_title

Blood

authors

Dietrich S,Hüllein J,Lee SC,Hutter B,Gonzalez D,Jayne S,Dyer MJ,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,Hafe

doi

10.1182/blood-2015-04-643361

subject

Has Abstract

pub_date

2015-08-20 00:00:00

pages

1005-8

issue

8

eissn

0006-4971

issn

1528-0020

pii

blood-2015-04-643361

journal_volume

126

pub_type

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