Associação Portuguesa de Investigação em Cancro
KIAA1549:BRAF fusion and FGFR1 mutations: prognostic in pilocytic astrocytomas
KIAA1549:BRAF fusion and FGFR1 mutations: prognostic in pilocytic astrocytomas
Authors and Affiliations:
Aline Paixão Becker1,7, Cristovam Scapulatempo-Neto2, Adriana C. Carloni1, Alessandra Paulino1, Jamie Sheren3, Dara L. Aisner3, Evelyn Musselwhite4, Carlos Clara5, Hélio R. Machado6, Ricardo S. Oliveira6, Luciano Neder7, Marileila Varella-Garcia4, Rui M Reis1,8,9
1 Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil;
2 Department of Pathology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil;
3 University of Colorado Cancer Center, Aurora, CO, USA;
4 University of Colorado School of Medicine, Aurora, CO, USA;
5 Department of Neurosurgery, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
6 Department of Surgery at Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP);
7 Department of Pathology and Forensic Medicine at Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP);
8 Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal;
9 ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Abstract:
Up to 20% of the patients with pilocytic astrocytoma (PA) experience poor outcome. BRAF alterations and FGFR1 point mutations are key molecular alterations in PAs, but their clinical implications are not established. We aimed to determine the frequency and prognostic role of these alterations in a cohort of 69 patients with PAs. We assessed KIAA1549:BRAF fusion by FISH and BRAF (exon 15) mutations by capillary sequencing. In addition, FGFR1 immunohistochemical expression was analyzed and compared to gene amplification and hotspot mutations (exons 12 and 14) assessed by FISH and capillary sequencing. KIAA1549:BRAF fusion was seen in almost 60% of cases. Two tumors harbored mutated BRAF. Despite the overall FGFR1 expression, no cases depicted FGFR1 amplifications. Three cases harboured FGFR1 p.K656E point mutation. No correlation was observed between BRAF and FGFR1 alterations. The cases were predominantly pediatric (87 %), and no statistical differences were observed in molecular alterations between patients’ age context. We confirmed the high frequency of KIAA1549:BRAF fusion in PAs and its association with better outcome. Oncogenic mutations of FGFR1, though rare, occurred in a subset of patients with worse outcome. These molecular alterations may constitute alternative targets for novel clinical approaches, when radical surgical resection is unachievable.
Journal: Journal of Neuropathology and Experimental Neurology
