RNA-binding protein (RBFOX1) inherited polymorphism rs8051518 is not associated with splice factor mutations in myelodysplastic syndromes and myeloproliferative neoplasms
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In recent years, many DNA polymorphisms were linked to the risk of tumor development or poor outcome in cancer patients [1, 2, 3]. Large publicly available datasets of whole exome and whole genome sequencing projects like The Cancer Genome Atlas (TCGA) or the International Cancer Genome Consortium (ICGC) enable the analysis of polymorphisms in thousands of cancer patients in silico. In a very detailed work, Carter et al.  analyzed nearly 6000 cancer patients from the TCGA and ICGC databases and found over 400 genetic interactions between germline polymorphisms and major somatic events, like mutations in driver genes. One noteworthy interaction is an 8-fold increase of SF3B1 mutations when a germline variant in intron 4 (rs8051518) of the RNA-binding protein (RBFOX1) was present. Furthermore, the authors showed an increase of RBFOX1mRNA expression and differentially spliced exon-exon junctions in the presence of the minor allele (rs8051518). This interaction is...
Compliance with ethical standards
The study was approved by the Ethics Committee of Hannover Medical School
Conflict of interest
The authors declare that they have no conflict of interest.
- 3.Liu W, He L, Ramírez J, Krishnaswamy S, Kanteti R, Wang Y, Salgia R, Ratain MJ (2011) Functional EGFR germline polymorphisms may confer risk for EGFR somatic mutations in non-small cell lung cancer, with a predominant effect on exon 19 microdeletions. Cancer Res 71:2423–2427. https://doi.org/10.1158/0008-5472.CAN-10-2689 CrossRefPubMedPubMedCentralGoogle Scholar
- 4.Carter H, Marty R, Hofree M, Gross AM, Jensen J, Fisch KM, Wu X, DeBoever C, Van Nostrand EL, Song Y, Wheeler E, Kreisberg JF, Lippman SM, Yeo GW, Gutkind JS, Ideker T (2017) Interaction landscape of inherited polymorphisms with somatic events in Cancer. Cancer Discov 7:410–423. https://doi.org/10.1158/2159-8290.CD-16-1045 CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Arber DA, Orazi A, Hasserjian R, Thiele J, Browitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127:2391–2405. https://doi.org/10.1182/blood-2016-03-643544 CrossRefPubMedGoogle Scholar
- 6.Bartels S, Schipper E, Hasemeier B, Kreipe H, Lehmann U (2016) Routine clinical mutation profiling using next generation sequencing and a customized gene panel improves diagnostic precision in myeloid neoplasms. Oncotarget. https://doi.org/10.18632/oncotarget.8310
- 7.Bartels S, Lehmann U (2015) Analysis of mutational hotspots in routinely processed bone marrow trephines by pyrosequencing®. Methods Mol Biol. https://doi.org/10.1007/978-1-4939-2715-9_8
- 8.Klinck R, Fourrier A, Thibault P, Toutant J, Durand M, Lapointe E, Caillet-Boudin ML, Sergeant N, Gourdon G, Meola G, Furling D, Puymirat J, Chabot B (2014) RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1. PLoS One 9:e107324. https://doi.org/10.1371/journal.pone.0107324 CrossRefPubMedPubMedCentralGoogle Scholar