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
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