A Novel JAK2 Exon 12 Mutation Identified in the Retrospective Analysis of Paraffin-embedded Tissues of Polycythemia Vera Patients

被引:4
作者
Buijanivova, Tatiana [1 ]
Marcinek, Juraj
Lasabova, Zora [2 ]
Minarik, Gabriel [3 ]
Szepe, Peter
Balharek, Tomas
Vanochova, Andrea [2 ]
Polacek, Hubert
Plank, Lukas
机构
[1] Fac Hosp Martin, Dept Pathol, Martin 03659, Slovakia
[2] Comenius Univ, Dept Mol Biol, Jessenius Fac Med, Martin, Slovakia
[3] Comenius Univ, Dept Mol Biol, Fac Nat Sci, Bratislava, Slovakia
关键词
JAK2; exon; 12; mutations; paraffin-embedded tissues; polycythemia vera; TYROSINE KINASE JAK2; MYELOPROLIFERATIVE DISORDERS; V617F MUTATION; IDIOPATHIC ERYTHROCYTOSIS; ESSENTIAL THROMBOCYTHEMIA; BONE-MARROW;
D O I
10.1097/PDM.0b013e318190eed0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The aim of the study was to screen formalin-fixed, paraffin-embedded tissues of polycythemia vera patients for the presence of JAK2(V617F) and JAK2 exon 12 mutations. Of 64 cases, 60 were positive for JAK2(V617F) mutation using allele-specific polymerase chain reaction (PCR). Using modified allele-specific PCR, samples of 4 JAK2(V617F)-negative patients were analyzed for the presence of JAK2 exon 12 Mutations. In one case, we found a PCR product matching with allele-specific primer, which was designed to detect the N542-E543del mutation. Surprisingly, in the result sequence we have detected another recently described Mutation, R541-E543delinsK. In the other 3 JAK2(V617F)-negative patients, allele-specific PCR for the detection of JAK2 exon 12 mutations did not yield any product. However, in I case, the sequencing of JAK2 exon 12 PCR product revealed a novel mutation, H538-K539delinsF. We confirmed that paraffin-embedded tissues represent a valuable source of DNA, which can be used in diagnostics of both JAK2 exon 12 and exon 14 Mutations and we described I novel JAK2 exon 12 mutation.
引用
收藏
页码:108 / 111
页数:4
相关论文
共 14 条
[1]   Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders [J].
Baxter, EJ ;
Scott, LM ;
Campbell, PJ ;
East, C ;
Fourouclas, N ;
Swanton, S ;
Vassiliou, GS ;
Bench, AJ ;
Boyd, EM ;
Curtin, N ;
Scott, MA ;
Erber, WN ;
Green, AR .
LANCET, 2005, 365 (9464) :1054-1061
[2]   Two novel JAK2 exon 12 mutations in JAK2V617F-negative polycythaemia vera patients [J].
Butcher, C. M. ;
Hahn, U. ;
To, L. B. ;
Gecz, J. ;
Wilkins, E. J. ;
Scott, H. S. ;
Bardy, P. G. ;
D'Andrea, R. J. .
LEUKEMIA, 2008, 22 (04) :870-873
[3]   Somatic mutations of JAK2 exon 12 as a molecular basis of erythrocytosis [J].
Cazzola, Mario .
HAEMATOLOGICA, 2007, 92 (12) :1585-+
[4]   Detecting the JAK2 V617F mutation in fresh and 'historic' blood and bone marrow [J].
Gattenlohner, S. ;
Peter, C. ;
Bonengel, M. ;
Einsele, H. ;
Bargou, R. ;
Muller-Hermelink, H-K ;
Marx, A. .
LEUKEMIA, 2007, 21 (07) :1599-1602
[5]   Detection of the activating JAK2 V617F mutation in paraffin-embedded trephine bone marrow biopsies of patients with chronic myeloproliferative diseases [J].
Horn, Thomas ;
Kremer, Marcus ;
Dechow, Tobias ;
Pfeifer, Walther M. ;
Geist, Birgit ;
Perker, Michael ;
Duyster, Justus ;
Quintanilla-Martinez, Leticia ;
Fend, Falko .
JOURNAL OF MOLECULAR DIAGNOSTICS, 2006, 8 (03) :299-304
[6]   A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera [J].
James, C ;
Ugo, V ;
Le Couédic, JP ;
Staerk, J ;
Delhommeau, F ;
Lacout, C ;
Garçon, L ;
Raslova, H ;
Berger, R ;
Bennaceur-Griscelli, A ;
Villeval, JL ;
Constantinescu, SN ;
Casadevall, N ;
Vainchenker, W .
NATURE, 2005, 434 (7037) :1144-1148
[7]   Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders [J].
Jones, AV ;
Kreil, S ;
Zoi, K ;
Waghorn, K ;
Curtis, C ;
Zhang, LY ;
Score, J ;
Seear, R ;
Chase, AJ ;
Grand, FH ;
White, H ;
Zoi, C ;
Loukopoulos, D ;
Terpos, E ;
Vervessou, EC ;
Schultheis, B ;
Emig, M ;
Ernst, T ;
Lengfelder, E ;
Hehlmann, R ;
Hochhaus, A ;
Oscier, D ;
Silver, RT ;
Reiter, A ;
Cross, NCP .
BLOOD, 2005, 106 (06) :2162-2168
[8]   A gain-of-function mutation of JAK2 in myeloproliferative disorders [J].
Kralovics, R ;
Passamonti, F ;
Buser, AS ;
Teo, S ;
Tiedt, R ;
Passweg, JR ;
Tichelli, A ;
Cazzola, M ;
Skoda, RC .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (17) :1779-1790
[9]   Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis [J].
Levine, RL ;
Wadleigh, M ;
Cools, J ;
Ebert, BL ;
Wernig, G ;
Huntly, BJP ;
Boggon, TJ ;
Wlodarska, L ;
Clark, JJ ;
Moore, S ;
Adelsperger, J ;
Koo, S ;
Lee, JC ;
Gabriel, S ;
Mercher, T ;
D'Andrea, A ;
Fröhling, S ;
Döhner, K ;
Marynen, P ;
Vandenberghe, P ;
Mesa, RA ;
Tefferi, A ;
Griffin, JD ;
Eck, MJ ;
Sellers, WR ;
Meyerson, M ;
Golub, TR ;
Lee, SJ ;
Gilliland, DG .
CANCER CELL, 2005, 7 (04) :387-397
[10]   Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders [J].
Levine, Ross L. ;
Pardanani, Animesh ;
Tefferi, Ayalew ;
Gilliland, D. Gary .
NATURE REVIEWS CANCER, 2007, 7 (09) :673-683