Mosquera Orgueira, AdriánAlonso Vence, NataliaDíaz Arias, José ÁngelAntelo Rodríguez, BeatrizDíaz Varela, Nicolás AntonioPérez Encinas, Manuel MateoAllegue Toscano, CatarinaGoiricelaya Seco, Elena MaríaCarracedo Álvarez, ÁngelBello López, José Luis2020-04-232020-04-232019Mosquera 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-y1471-2407http://hdl.handle.net/10347/21674Background 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. Methods 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. Results 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. Conclusion 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.eng© The Author(s). 2019. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedhttps://creativecommons.org/licenses/by/4.0/Chronic lymphocytic leukemiaGermlinePolymorphismAssociationPrognosisjournal article10.1186/s12885-019-5628-yopen access