Back to Search Start Over

The association of germline variants with chronic lymphocytic leukemia outcome suggests the implication of novel genes and pathways in clinical evolution.

Authors :
Mosquera Orgueira, Adrián
Antelo Rodríguez, Beatriz
Alonso Vence, Natalia
Díaz Arias, José Ángel
Díaz Varela, Nicolás
Pérez Encinas, Manuel Mateo
Allegue Toscano, Catarina
Goiricelaya Seco, Elena María
Carracedo Álvarez, Ángel
Bello López, José Luis
Source :
BMC Cancer. 5/29/2019, Vol. 19 Issue 1, p1-11. 11p. 4 Charts, 4 Graphs.
Publication Year :
2019

Abstract

<bold>Background: </bold>Chronic Lymphocytic Leukemia (CLL) is the most frequent lymphoproliferative disorder in western countries and is characterized by a remarkable clinical heterogeneity. During the last decade, multiple genomic studies have identified a myriad of somatic events driving CLL proliferation and aggressivity. Nevertheless, and despite the mounting evidence of inherited risk for CLL development, the existence of germline variants associated with clinical outcomes has not been addressed in depth.<bold>Methods: </bold>Exome sequencing data from control leukocytes of CLL patients involved in the International Cancer Genome Consortium (ICGC) was used for genotyping. Cox regression was used to detect variants associated with clinical outcomes. Gene and pathways level associations were also calculated.<bold>Results: </bold>Single nucleotide polymorphisms in PPP4R2 and MAP3K4 were associated with earlier treatment need. A gene-level analysis evidenced a significant association of RIPK3 with both treatment need and survival. Furthermore, germline variability in pathways such as apoptosis, cell-cycle, pentose phosphate, GNα13 and Nitric oxide was associated with overall survival.<bold>Conclusion: </bold>Our results support the existence of inherited conditionants of CLL evolution and points towards genes and pathways that may results useful as biomarkers of disease outcome. More research is needed to validate these findings. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14712407
Volume :
19
Issue :
1
Database :
Academic Search Index
Journal :
BMC Cancer
Publication Type :
Academic Journal
Accession number :
136713732
Full Text :
https://doi.org/10.1186/s12885-019-5628-y