Identification of Clinically Relevant Subgroups of Chronic
Lymphocytic Leukemia Through Discovery of Abnormal Molecular
Pathways

J 2021

Identification of Clinically Relevant Subgroups of Chronic Lymphocytic Leukemia Through Discovery of Abnormal Molecular Pathways

TAUŠ, Petr, Šárka POSPÍŠILOVÁ and Karla PLEVOVÁ

Basic information

Original name

Identification of Clinically Relevant Subgroups of Chronic Lymphocytic Leukemia Through Discovery of Abnormal Molecular Pathways

Authors

TAUŠ, Petr (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution) and Karla PLEVOVÁ (203 Czech Republic, belonging to the institution)

Edition

Frontiers in Genetics, Laussane, FRONTIERS MEDIA SA, 2021, 1664-8021

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10603 Genetics and heredity

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.772

RIV identification code

RIV/00216224:14740/21:00120186

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.3389/fgene.2021.627964

UT WoS

000671833200001

Keywords in English

chronic lymphocytic leukemia; pathway mutation score; ensemble clustering; extreme gradient boosting; mutation subtypes

Abstract

V originále

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western world with a highly variable clinical course. Its striking genetic heterogeneity is not yet fully understood. Although the CLL genetic landscape has been well-described, patient stratification based on mutation profiles remains elusive mainly due to the heterogeneity of data. Here we attempted to decrease the heterogeneity of somatic mutation data by mapping mutated genes in the respective biological processes. From the sequencing data gathered by the International Cancer Genome Consortium for 506 CLL patients, we generated pathway mutation scores, applied ensemble clustering on them, and extracted abnormal molecular pathways with a machine learning approach. We identified four clusters differing in pathway mutational profiles and time to first treatment. Interestingly, common CLL drivers such as ATM or TP53 were associated with particular subtypes, while others like NOTCH1 or SF3B1 were not. This study provides an important step in understanding mutational patterns in CLL.

Links

LM2018140, research and development project

Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/A/1595/2020, interní kód MU

Name: Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit VIII (Acronym: VýDiTeHeMa VIII)

Investor: Masaryk University

NU21-08-00237, research and development project

Name: Pokročilé sekvenační metody pro analýzu strukturních přestaveb nádorového genomu

Investor: Ministry of Health of the CR, Advanced sequencing methods for deciphering structural variants in cancer genome, Subprogram 1 - standard

Citovat

TAUŠ, Petr, Šárka POSPÍŠILOVÁ and Karla PLEVOVÁ. Identification of Clinically Relevant Subgroups of Chronic Lymphocytic Leukemia Through Discovery of Abnormal Molecular Pathways. Frontiers in Genetics. Laussane: FRONTIERS MEDIA SA, 2021, vol. 12, JUN, p. 627964-627973. ISSN 1664-8021. Available from: https://dx.doi.org/10.3389/fgene.2021.627964.

@article{1813393,
   author = {Tauš, Petr and Pospíšilová, Šárka and Plevová, Karla},
   article_location = {Laussane},
   article_number = {JUN},
   doi = {http://dx.doi.org/10.3389/fgene.2021.627964},
   keywords = {chronic lymphocytic leukemia; pathway mutation score; ensemble clustering; extreme gradient boosting; mutation subtypes},
   language = {eng},
   issn = {1664-8021},
   journal = {Frontiers in Genetics},
   title = {Identification of Clinically Relevant Subgroups of Chronic Lymphocytic Leukemia Through Discovery of Abnormal Molecular Pathways},
   url = {https://www.frontiersin.org/articles/10.3389/fgene.2021.627964/full},
   volume = {12},
   year = {2021}
}

TY  - JOUR
ID  - 1813393
AU  - Tauš, Petr - Pospíšilová, Šárka - Plevová, Karla
PY  - 2021
TI  - Identification of Clinically Relevant Subgroups of Chronic Lymphocytic Leukemia Through Discovery of Abnormal Molecular Pathways
JF  - Frontiers in Genetics
VL  - 12
IS  - JUN
SP  - 627964
EP  - 627964
PB  - FRONTIERS MEDIA SA
SN  - 16648021
KW  - chronic lymphocytic leukemia
KW  - pathway mutation score
KW  - ensemble clustering
KW  - extreme gradient boosting
KW  - mutation subtypes
UR  - https://www.frontiersin.org/articles/10.3389/fgene.2021.627964/full
N2  - Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western world with a highly variable clinical course. Its striking genetic heterogeneity is not yet fully understood. Although the CLL genetic landscape has been well-described, patient stratification based on mutation profiles remains elusive mainly due to the heterogeneity of data. Here we attempted to decrease the heterogeneity of somatic mutation data by mapping mutated genes in the respective biological processes. From the sequencing data gathered by the International Cancer Genome Consortium for 506 CLL patients, we generated pathway mutation scores, applied ensemble clustering on them, and extracted abnormal molecular pathways with a machine learning approach. We identified four clusters differing in pathway mutational profiles and time to first treatment. Interestingly, common CLL drivers such as ATM or TP53 were associated with particular subtypes, while others like NOTCH1 or SF3B1 were not. This study provides an important step in understanding mutational patterns in CLL.
ER  -

TAUŠ, Petr, Šárka POSPÍŠILOVÁ and Karla PLEVOVÁ. Identification of Clinically Relevant Subgroups of Chronic Lymphocytic Leukemia Through Discovery of Abnormal Molecular Pathways. \textit{Frontiers in Genetics}. Laussane: FRONTIERS MEDIA SA, 2021, vol.~12, JUN, p.~627964-627973. ISSN~1664-8021. Available from: https://dx.doi.org/10.3389/fgene.2021.627964.

Detailed Information on Publication Record