Identification and functional characterization of new missense
SNPs in the coding region of the TP53 gene

J 2021

Identification and functional characterization of new missense SNPs in the coding region of the TP53 gene

DOFFE, Flora, Vincent CARBONNIER, Manon TISSIER, Bernard LEROY, Isabelle MARTINS et. al.

Základní údaje

Originální název

Identification and functional characterization of new missense SNPs in the coding region of the TP53 gene

Autoři

DOFFE, Flora, Vincent CARBONNIER, Manon TISSIER, Bernard LEROY, Isabelle MARTINS, Johanna S. M. MATTSSON, Patrick MICKE, Šárka PAVLOVÁ (203 Česká republika, domácí), Šárka POSPÍŠILOVÁ (203 Česká republika, domácí), Jana ŠMARDOVÁ (203 Česká republika, domácí), Andreas C. JOERGER, Klas G. WIMAN, Guido KROEMER a Thierry SOUSSI

Vydání

Cell Death and Differentiation, London, Springer Nature, 2021, 1350-9047

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30205 Hematology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 12.067

Kód RIV

RIV/00216224:14740/21:00118820

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1038/s41418-020-00672-0

UT WoS

000594811400001

Klíčová slova anglicky

Genetics research; Tumour-suppressor proteins

Štítky

14110212, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 4. 2022 14:04, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Infrequent and rare genetic variants in the human population vastly outnumber common ones. Although they may contribute significantly to the genetic basis of a disease, these seldom-encountered variants may also be miss-identified as pathogenic if no correct references are available. Somatic and germline TP53 variants are associated with multiple neoplastic diseases, and thus have come to serve as a paradigm for genetic analyses in this setting. We searched 14 independent, globally distributed datasets and recovered TP53 SNPs from 202,767 cancer-free individuals. In our analyses, 19 new missense TP53 SNPs, including five novel variants specific to the Asian population, were recurrently identified in multiple datasets. Using a combination of in silico, functional, structural, and genetic approaches, we showed that none of these variants displayed loss of function compared to the normal TP53 gene. In addition, classification using ACMG criteria suggested that they are all benign. Considered together, our data reveal that the TP53 coding region shows far more polymorphism than previously thought and present high ethnic diversity. They furthermore underline the importance of correctly assessing novel variants in all variant-calling pipelines associated with genetic diagnoses for cancer.

Návaznosti

GA19-15737S, projekt VaV

Název: Alternativní mechanismy deregulace p53 dráhy u chronické lymfocytární leukémie

Investor: Grantová agentura ČR, Alternativní mechanismy deregulace p53 dráhy u chronické lymfocytární leukémie

Citovat

DOFFE, Flora, Vincent CARBONNIER, Manon TISSIER, Bernard LEROY, Isabelle MARTINS, Johanna S. M. MATTSSON, Patrick MICKE, Šárka PAVLOVÁ, Šárka POSPÍŠILOVÁ, Jana ŠMARDOVÁ, Andreas C. JOERGER, Klas G. WIMAN, Guido KROEMER a Thierry SOUSSI. Identification and functional characterization of new missense SNPs in the coding region of the TP53 gene. Cell Death and Differentiation. London: Springer Nature, 2021, roč. 28, č. 5, s. 1477-1492. ISSN 1350-9047. Dostupné z: https://dx.doi.org/10.1038/s41418-020-00672-0.

@article{1727497,
   author = {Doffe, Flora and Carbonnier, Vincent and Tissier, Manon and Leroy, Bernard and Martins, Isabelle and Mattsson, Johanna S. M. and Micke, Patrick and Pavlová, Šárka and Pospíšilová, Šárka and Šmardová, Jana and Joerger, Andreas C. and Wiman, Klas G. and Kroemer, Guido and Soussi, Thierry},
   article_location = {London},
   article_number = {5},
   doi = {http://dx.doi.org/10.1038/s41418-020-00672-0},
   keywords = {Genetics research; Tumour-suppressor proteins},
   language = {eng},
   issn = {1350-9047},
   journal = {Cell Death and Differentiation},
   title = {Identification and functional characterization of new missense SNPs in the coding region of the TP53 gene},
   url = {https://doi.org/10.1038/s41418-020-00672-0},
   volume = {28},
   year = {2021}
}

TY  - JOUR
ID  - 1727497
AU  - Doffe, Flora - Carbonnier, Vincent - Tissier, Manon - Leroy, Bernard - Martins, Isabelle - Mattsson, Johanna S. M. - Micke, Patrick - Pavlová, Šárka - Pospíšilová, Šárka - Šmardová, Jana - Joerger, Andreas C. - Wiman, Klas G. - Kroemer, Guido - Soussi, Thierry
PY  - 2021
TI  - Identification and functional characterization of new missense SNPs in the coding region of the TP53 gene
JF  - Cell Death and Differentiation
VL  - 28
IS  - 5
SP  - 1477-1492
EP  - 1477-1492
PB  - Springer Nature
SN  - 13509047
KW  - Genetics research
KW  - Tumour-suppressor proteins
UR  - https://doi.org/10.1038/s41418-020-00672-0
L2  - https://doi.org/10.1038/s41418-020-00672-0
N2  - Infrequent and rare genetic variants in the human population vastly outnumber common ones. Although they may contribute significantly to the genetic basis of a disease, these seldom-encountered variants may also be miss-identified as pathogenic if no correct references are available. Somatic and germline TP53 variants are associated with multiple neoplastic diseases, and thus have come to serve as a paradigm for genetic analyses in this setting. We searched 14 independent, globally distributed datasets and recovered TP53 SNPs from 202,767 cancer-free individuals. In our analyses, 19 new missense TP53 SNPs, including five novel variants specific to the Asian population, were recurrently identified in multiple datasets. Using a combination of in silico, functional, structural, and genetic approaches, we showed that none of these variants displayed loss of function compared to the normal TP53 gene. In addition, classification using ACMG criteria suggested that they are all benign. Considered together, our data reveal that the TP53 coding region shows far more polymorphism than previously thought and present high ethnic diversity. They furthermore underline the importance of correctly assessing novel variants in all variant-calling pipelines associated with genetic diagnoses for cancer.
ER  -

DOFFE, Flora, Vincent CARBONNIER, Manon TISSIER, Bernard LEROY, Isabelle MARTINS, Johanna S. M. MATTSSON, Patrick MICKE, Šárka PAVLOVÁ, Šárka POSPÍŠILOVÁ, Jana ŠMARDOVÁ, Andreas C. JOERGER, Klas G. WIMAN, Guido KROEMER a Thierry SOUSSI. Identification and functional characterization of new missense SNPs in the coding region of the TP53 gene. \textit{Cell Death and Differentiation}. London: Springer Nature, 2021, roč.~28, č.~5, s.~1477-1492. ISSN~1350-9047. Dostupné z: https://dx.doi.org/10.1038/s41418-020-00672-0.

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