Monoallelic and biallelic inactivation of TP53 gene in chronic
lymphocytic leukemia: selection, impact on survival, and
response to DNA damage.

J 2009

Monoallelic and biallelic inactivation of TP53 gene in chronic lymphocytic leukemia: selection, impact on survival, and response to DNA damage.

MALČÍKOVÁ, Jitka, Jana ŠMARDOVÁ, Ludmila ROČŇOVÁ, Boris TICHÝ, Petr KUGLÍK et. al.

Základní údaje

Originální název

Monoallelic and biallelic inactivation of TP53 gene in chronic lymphocytic leukemia: selection, impact on survival, and response to DNA damage.

Autoři

Vydání

Blood, Washington, DC, American Society of Hematology, 2009, 0006-4971

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 10.555

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1182/blood-2009-07-234708

UT WoS

000272863800011

Klíčová slova česky

CLL; TP53; inaktivace; FASAY; FISH

Klíčová slova anglicky

CLL; TP53; inactivation; FASAY; FISH

Příznaky

Mezinárodní význam

Změněno: 10. 4. 2012 11:37, Mgr. Michal Petr

Anotace

V originále

Deletion of TP53 gene, under routine assessment by fluorescence in situ hybridization analysis, connects with the worst prognosis in chronic lymphocytic leukemia (CLL). The presence of isolated TP53 mutation (without deletion) is associated with reduced survival in CLL patients. It is unclear how these abnormalities are selected and what their mutual proportion is. We used methodologies with similar sensitivity for the detection of deletions (interphase fluorescence in situ hybridization) and mutations (yeast functional analysis) and analyzed a large consecutive series of 400 CLL patients; a subset of p53-wild-type cases (n = 132) was screened repeatedly during disease course. The most common type of TP53 inactivation, ie, mutation accompanied by deletion of the remaining allele, occurred in 42 patients (10.5%). Among additional defects, the frequency of the isolated TP53 mutation (n = 20; 5%) and the combination of 2 or more mutations on separate alleles (n = 5; 1.3%) greatly exceeded the sole deletion (n = 3; 0.8%). Twelve patients manifested defects during repeated investigation; in all circumstances the defects involved mutation and occurred after therapy. Monoallelic defects had a negative impact on survival and impaired in vitro response to fludarabine. Mutation analysis of the TP53 should be performed before each treatment initiation because novel defects may be selected by previous therapies.

Návaznosti

MSM0021622430, záměr

Název: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Citovat

MALČÍKOVÁ, Jitka, Jana ŠMARDOVÁ, Ludmila ROČŇOVÁ, Boris TICHÝ, Petr KUGLÍK, Vladimíra VRANOVÁ, Soňa ČEJKOVÁ, Miluše SVITÁKOVÁ, Hana SKUHROVÁ FRANCOVÁ, Yvona BRYCHTOVÁ, Michael DOUBEK, Martin BREJCHA, Martin KLABUSAY, Jiří MAYER, Šárka POSPÍŠILOVÁ a Martin TRBUŠEK. Monoallelic and biallelic inactivation of TP53 gene in chronic lymphocytic leukemia: selection, impact on survival, and response to DNA damage. Blood. Washington, DC: American Society of Hematology, 2009, roč. 114, č. 26, s. 5307-5314. ISSN 0006-4971. Dostupné z: https://dx.doi.org/10.1182/blood-2009-07-234708.

@article{865962,
   author = {Malčíková, Jitka and Šmardová, Jana and Ročňová, Ludmila and Tichý, Boris and Kuglík, Petr and Vranová, Vladimíra and Čejková, Soňa and Svitáková, Miluše and Skuhrová Francová, Hana and Brychtová, Yvona and Doubek, Michael and Brejcha, Martin and Klabusay, Martin and Mayer, Jiří and Pospíšilová, Šárka and Trbušek, Martin},
   article_location = {Washington, DC},
   article_number = {26},
   doi = {http://dx.doi.org/10.1182/blood-2009-07-234708},
   keywords = {CLL; TP53; inactivation; FASAY; FISH},
   language = {eng},
   issn = {0006-4971},
   journal = {Blood},
   title = {Monoallelic and biallelic inactivation of TP53 gene in chronic lymphocytic leukemia: selection, impact on survival, and response to DNA damage.},
   volume = {114},
   year = {2009}
}

TY  - JOUR
ID  - 865962
AU  - Malčíková, Jitka - Šmardová, Jana - Ročňová, Ludmila - Tichý, Boris - Kuglík, Petr - Vranová, Vladimíra - Čejková, Soňa - Svitáková, Miluše - Skuhrová Francová, Hana - Brychtová, Yvona - Doubek, Michael - Brejcha, Martin - Klabusay, Martin - Mayer, Jiří - Pospíšilová, Šárka - Trbušek, Martin
PY  - 2009
TI  - Monoallelic and biallelic inactivation of TP53 gene in chronic lymphocytic leukemia: selection, impact on survival, and response to DNA damage.
JF  - Blood
VL  - 114
IS  - 26
SP  - 5307-5314
EP  - 5307-5314
PB  - American Society of Hematology
SN  - 00064971
KW  - CLL
KW  - TP53
KW  - inactivation
KW  - FASAY
KW  - FISH
N2  - Deletion of TP53 gene, under routine assessment by fluorescence in situ hybridization analysis, connects with the worst prognosis in chronic lymphocytic leukemia (CLL). The presence of isolated TP53 mutation (without deletion) is associated with reduced survival in CLL patients. It is unclear how these abnormalities are selected and what their mutual proportion is. We used methodologies with similar sensitivity for the detection of deletions (interphase fluorescence in situ hybridization) and mutations (yeast functional analysis) and analyzed a large consecutive series of 400 CLL patients; a subset of p53-wild-type cases (n = 132) was screened repeatedly during disease course. The most common type of TP53 inactivation, ie, mutation accompanied by deletion of the remaining allele, occurred in 42 patients (10.5%). Among additional defects, the frequency of the isolated TP53 mutation (n = 20; 5%) and the combination of 2 or more mutations on separate alleles (n = 5; 1.3%) greatly exceeded the sole deletion (n = 3; 0.8%). Twelve patients manifested defects during repeated investigation; in all circumstances the defects involved mutation and occurred after therapy. Monoallelic defects had a negative impact on survival and impaired in vitro response to fludarabine. Mutation analysis of the TP53 should be performed before each treatment initiation because novel defects may be selected by previous therapies.
ER  -

MALČÍKOVÁ, Jitka, Jana ŠMARDOVÁ, Ludmila ROČŇOVÁ, Boris TICHÝ, Petr KUGLÍK, Vladimíra VRANOVÁ, Soňa ČEJKOVÁ, Miluše SVITÁKOVÁ, Hana SKUHROVÁ FRANCOVÁ, Yvona BRYCHTOVÁ, Michael DOUBEK, Martin BREJCHA, Martin KLABUSAY, Jiří MAYER, Šárka POSPÍŠILOVÁ a Martin TRBUŠEK. Monoallelic and biallelic inactivation of TP53 gene in chronic lymphocytic leukemia: selection, impact on survival, and response to DNA damage. \textit{Blood}. Washington, DC: American Society of Hematology, 2009, roč.~114, č.~26, s.~5307-5314. ISSN~0006-4971. Dostupné z: https://dx.doi.org/10.1182/blood-2009-07-234708.

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