Informace o publikaci

Recurrent mutations refine prognosis in chronic lymphocytic leukemia.

Autoři	BALIAKAS P. HADZIDIMITRIOU A. SUTTON LA. ROSSI D. MINGA E. VILLAMOR N. LARRAYOZ M. KMÍNKOVÁ Jana AGATHANGELIDIS A. DAVIS Z. TAUSCH E. STALIKA E. KANTOROVÁ Barbara MANSOURI L. SCARFO L. CORTESE D. NAVRKALOVÁ Veronika ROSE-ZERILLI MJ. SMEDBY K.E. JULIUSSON G. ANAGNOSTOPOULOS A. MAKRIS A.M. NAVARRO A. DELGADO J. OSCIER D. BELESSI C. STILGENBAUER S. GHIA P. POSPÍŠILOVÁ Šárka GAIDANO G. CAMPO E. STREFFORD J.C. STAMATOPOULOS K. ROSENQUIST R.
Rok publikování	2015
Druh	Článek v odborném periodiku
Časopis / Zdroj	Leukemia
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	http://www.nature.com/leu/journal/vaop/ncurrent/pdf/leu2014196a.pdf
Doi	http://dx.doi.org/10.1038/leu.2014.196
Obor	Onkologie a hematologie
Klíčová slova	mutations; CLL; ERIC
Přiložené soubory	1216571_Recurrent_mutations_doplneni_projektu.pdf ZVV_2015_006_1216571_Reccuerent_mutations.pdf
Popis	Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n 1/4 3334), SF3B1 (n 1/4 2322), TP53 (n 1/4 2309), MYD88 (n 1/4 1080) and BIRC3 (n 1/4 919) genes, mainly at diagnosis (75%) and before treatment (490%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (Po0.0001) in 889 treatment-naive Binet stage A cases. In multivariate analysis (n 1/4 774), SF3B1 mutations and TP53ab along with del(11q) and U-CLL, but not NOTCH1 mutations, retained independent significance. Importantly, TP53ab and SF3B1 mutations had an adverse impact even in U-CLL. In conclusion, we support the clinical relevance of novel recurrent mutations in CLL, highlighting the adverse impact of SF3B1 and TP53 mutations, even independent of IGHV mutational status, thus underscoring the need for urgent standardization/harmonization of the detection methods.
Související projekty:	CEITEC - středoevropský technologický institut Zaměstnáním čerstvých absolventů doktorského studia k vědecké excelenci Molekulární charakterizace B buněčných receptorů a jejich vztah k evoluci genetických změn u chronické lymfocytární leukémie Next Generation Sequencing Platform for Targeted Personalized Therapy of Leukemia