TP53 mutation profile in chronic lymphocytic leukemia: evidence
for a disease specific profile from a comprehensive analysis of
268 mutations

J 2010

TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations

ZENZ, T.; D. VOLLMER; Martin TRBUŠEK; Jana ŠMARDOVÁ; A. BENNER et al.

Základní údaje

Originální název

TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations

Název česky

Profil TP53 mutací u chronické lymfocytární leukémie: průkaz CLL specifického profilu komplexní analýzou 268 mutací.

Autoři

Vydání

Leukemia, England, Nature Publishing Group, 2010, 0887-6924

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 8.966

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/10:00051668

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.1038/leu.2010.208

UT WoS

000285380900012

Klíčová slova anglicky

CLL; genetics; 17p deletion; p53; TP53 mutation

Příznaky

Mezinárodní význam

Změněno: 10. 4. 2012 08:44, Mgr. Michal Petr

Anotace

ORIG CZ

V originále

The TP53 mutation profile in chronic lymphocytic leukemia (CLL) and the correlation of TP53 mutations with allele status or associated molecular genetics are currently unknown. We performed a large mutation analysis of TP53 at four centers and characterized the pattern of TP53 mutations in CLL. We report on 268 mutations in 254 patients with CLL. Missense mutations appeared in 74% of cases compared with deletions and insertions (20%), nonsense (4%) and splice site (2%) mutations. The majority (243 of 268) of mutations were located in the DNA-binding domain. Transitions were found in 131 of 268 mutations, with only 41 occurring at methylated CpG sites (15%), suggesting that transitions at CpGs are uncommon. The codons most frequently mutated were at positions 175, 179, 248 and 273; in addition, we detected a common 2-nt deletion in the codon 209. Most mutations (199 of 259) were accompanied by deletion of the other allele (17p-). Interestingly, trisomy 12 (without 17p-) was only found in one of 60 cases with TP53 mutation (without 17p-) compared with 60 of 16 in the cohort without mutation (P=0.006). The mutational profile was not different in the cohorts with and without previous therapy, suggesting that the mechanism underlying the development of mutations may be similar, independent of treatment.

Česky

U chronické lymfocytární leukémie (CLL) dosud nebyl popsán mutační profil TP53 mutací ani korelace TP53 mutací s alelovým statusem a molekulární genetikou. Provedli jsme mutační analýzu genu TP53 u pacientů ze čtyř center a charakterizovali jsme profil mutací u CLL. Celkem jsme popsali 268 mutací u 254 pacientů.

Citovat

ZENZ, T.; D. VOLLMER; Martin TRBUŠEK; Jana ŠMARDOVÁ; A. BENNER; T. SOUSSI; H. HELFRICH; M. HEUBERGER; P. HOTH; M. FUGE; T. DENZEL; S. HÄBE; Jitka MALČÍKOVÁ; Petr KUGLÍK; S. TRUONG; N. PATTEN; L. WU; D. OSCIER; R. IBBOTSON; A. GARDINER; I. TRACY; K. LIN; A. PETTITT; Šárka POSPÍŠILOVÁ; Jiří MAYER; M. HALLEK; H. DÖHNER a S. STILGENBAUER. TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations. Leukemia. England: Nature Publishing Group, 2010, roč. 24, č. 12, s. 2072-2079. ISSN 0887-6924. Dostupné z: https://doi.org/10.1038/leu.2010.208.

@article{918784,
   author = {Zenz, T. and Vollmer, D. and Trbušek, Martin and Šmardová, Jana and Benner, A. and Soussi, T. and Helfrich, H. and Heuberger, M. and Hoth, P. and Fuge, M. and Denzel, T. and Häbe, S. and Malčíková, Jitka and Kuglík, Petr and Truong, S. and Patten, N. and Wu, L. and Oscier, D. and Ibbotson, R. and Gardiner, A. and Tracy, I. and Lin, K. and Pettitt, A. and Pospíšilová, Šárka and Mayer, Jiří and Hallek, M. and Döhner, H. and Stilgenbauer, S.},
   article_location = {England},
   article_number = {12},
   doi = {https://doi.org/10.1038/leu.2010.208},
   keywords = {CLL; genetics; 17p deletion; p53; TP53 mutation},
   language = {eng},
   issn = {0887-6924},
   journal = {Leukemia},
   title = {TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations},
   volume = {24},
   year = {2010}
}

TY  - JOUR
ID  - 918784
AU  - Zenz, T. - Vollmer, D. - Trbušek, Martin - Šmardová, Jana - Benner, A. - Soussi, T. - Helfrich, H. - Heuberger, M. - Hoth, P. - Fuge, M. - Denzel, T. - Häbe, S. - Malčíková, Jitka - Kuglík, Petr - Truong, S. - Patten, N. - Wu, L. - Oscier, D. - Ibbotson, R. - Gardiner, A. - Tracy, I. - Lin, K. - Pettitt, A. - Pospíšilová, Šárka - Mayer, Jiří - Hallek, M. - Döhner, H. - Stilgenbauer, S.
PY  - 2010
TI  - TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations
JF  - Leukemia
VL  - 24
IS  - 12
SP  - 2072-2079
EP  - 2072-2079
PB  - Nature Publishing Group
SN  - 08876924
KW  - CLL
KW  - genetics
KW  - 17p deletion
KW  - p53
KW  - TP53 mutation
N2  - The TP53 mutation profile in chronic lymphocytic leukemia (CLL) and the correlation of TP53 mutations with allele status or associated molecular genetics are currently unknown. We performed a large mutation analysis of TP53 at four centers and characterized the pattern of TP53 mutations in CLL. We report on 268 mutations in 254 patients with CLL. Missense mutations appeared in 74% of cases compared with deletions and insertions (20%), nonsense (4%) and splice site (2%) mutations. The majority (243 of 268) of mutations were located in the DNA-binding domain. Transitions were found in 131 of 268 mutations, with only 41 occurring at methylated CpG sites (15%), suggesting that transitions at CpGs are uncommon. The codons most frequently mutated were at positions 175, 179, 248 and 273; in addition, we detected a common 2-nt deletion in the codon 209. Most mutations (199 of 259) were accompanied by deletion of the other allele (17p-). Interestingly, trisomy 12 (without 17p-) was only found in one of 60 cases with TP53 mutation (without 17p-) compared with 60 of 16 in the cohort without mutation (P=0.006). The mutational profile was not different in the cohorts with and without previous therapy, suggesting that the mechanism underlying the development of mutations may be similar, independent of treatment.
ER  -

ZENZ, T.; D. VOLLMER; Martin TRBUŠEK; Jana ŠMARDOVÁ; A. BENNER; T. SOUSSI; H. HELFRICH; M. HEUBERGER; P. HOTH; M. FUGE; T. DENZEL; S. HÄBE; Jitka MALČÍKOVÁ; Petr KUGLÍK; S. TRUONG; N. PATTEN; L. WU; D. OSCIER; R. IBBOTSON; A. GARDINER; I. TRACY; K. LIN; A. PETTITT; Šárka POSPÍŠILOVÁ; Jiří MAYER; M. HALLEK; H. DÖHNER a S. STILGENBAUER. TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations. \textit{Leukemia}. England: Nature Publishing Group, 2010, roč.~24, č.~12, s.~2072-2079. ISSN~0887-6924. Dostupné z: https://doi.org/10.1038/leu.2010.208.

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