Dysregulation of oncogenic factors by GFI1B p32: investigation of a novel <I>GFI1B</I> germline mutation
Michela Faleschini,
Nicole Papa,
Marie-Christine Morel-Kopp,
Caterina Marconi,
Tania Giangregorio,
Federica Melazzini,
Valeria Bozzi,
Marco Seri,
Patrizia Noris,
Alessandro Pecci,
Anna Savoia,
Roberta Bottega
Affiliations
Michela Faleschini
Institute for Maternal and Child Health – IRCCS Burlo Garofolo, Trieste
Nicole Papa
Institute for Maternal and Child Health – IRCCS Burlo Garofolo, Trieste
Marie-Christine Morel-Kopp
Department of Haematology and Transfusion Medicine, Royal North Shore Hospital and Northern Blood Research Centre, Kolling Institute, University of Sydney, Sydney
Caterina Marconi
Department of Medical and Surgical Sciences, University of Bologna, Bologna
Tania Giangregorio
Institute for Maternal and Child Health – IRCCS Burlo Garofolo, Trieste
Federica Melazzini
Biotechnology Research Laboratories, IRCCS Policlinico San Matteo Foundation, Pavia
Valeria Bozzi
Biotechnology Research Laboratories, IRCCS Policlinico San Matteo Foundation, Pavia
Marco Seri
Department of Medical and Surgical Sciences, University of Bologna, Bologna
Patrizia Noris
Biotechnology Research Laboratories, IRCCS Policlinico San Matteo Foundation, Pavia
Alessandro Pecci
Biotechnology Research Laboratories, IRCCS Policlinico San Matteo Foundation, Pavia
Anna Savoia
Institute for Maternal and Child Health – IRCCS Burlo Garofolo, Trieste, Italy; Department of Medical Sciences, University of Trieste, Trieste
Roberta Bottega
Institute for Maternal and Child Health – IRCCS Burlo Garofolo, Trieste
GFI1B is a transcription factor essential for the regulation of erythropoiesis and megakaryopoiesis, and pathogenic variants have been associated with thrombocytopenia and bleeding. Analysing thrombocytopenic families by whole exome sequencing, we identified a novel GFI1B variant (c.648+5G>A), which causes exon 9 skipping and overexpression of a shorter p32 isoform. We report the clinical data of our patients and critically review the phenotype observed in individuals with different GFI1B variants leading to the same effect on the p32 expression. Since p32 is increased in acute and chronic leukemia cells, we tested the expression level of genes playing a role in various type of cancers, including hematological tumors and found that they are significantly dysregulated, suggesting a potential role for GFI1B in carcinogenesis regulation. Increasing the detection of individuals with GFI1B variants will allow us to better characterize this rare disease and determine whether it is associated with an increased risk of developing malignancies.