RT Journal Article
T1 The association of germline variants with chronic lymphocytic leukemia outcome suggests the implication of novel genes and pathways in clinical evolution
A1 Mosquera Orgueira, Adrián
A1 Alonso Vence, Natalia
A1 Díaz Arias, José Ángel
A1 Antelo Rodríguez, Beatriz
A1 Díaz Varela, Nicolás Antonio
A1 Pérez Encinas, Manuel Mateo
A1 Allegue Toscano, Catarina
A1 Goiricelaya Seco, Elena María
A1 Carracedo Álvarez, Ángel
A1 Bello López, José Luis
K1 Chronic lymphocytic leukemia
K1 Germline
K1 Polymorphism
K1 Association
K1 Prognosis
AB BackgroundChronic 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.MethodsExome 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.ResultsSingle 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.ConclusionOur 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.
PB BMC
SN 1471-2407
YR 2019
FD 2019
LK http://hdl.handle.net/10347/21674
UL http://hdl.handle.net/10347/21674
LA eng
NO Mosquera Orgueira, A., Antelo Rodríguez, B., Alonso Vence, N. et al. The association of germline variants with chronic lymphocytic leukemia outcome suggests the implication of novel genes and pathways in clinical evolution. BMC Cancer 19, 515 (2019). https://doi.org/10.1186/s12885-019-5628-y
DS Minerva
RD 23 abr 2026