Abstract

Case Report

A novel case of an infantile fibrosarcoma-like tumor with KIAA1549-BRAF translocation and an oncogenic NF2p.Q459* SNV with potential clinical significance

Anita Nagy, Consolato M Sergi, Joseph de Nanassy, Lesleigh S Abbot, Anthony Arnoldo, Cynthia Hawkins and Bo-Yee Ngan*

Published: 27 August, 2021 | Volume 5 - Issue 1 | Pages: 016-019

We report a case of a right gluteal mass from the sacroiliac joint to the knee of an infant girl. Biopsy showed histopathological features similar to infantile fibrosarcoma (IFS). However, unlike most IFS, no ETV6-NTRK3 fusion gene abnormality was detected. Molecular analysis with TruSight RNA Pan-Cancer Panel detected the presence of KIAA1549-BRAF translocation and an oncogenic NF2p.Q459* SNV with potential clinical significance. A review revealed that the combination of this patient’s tumor site with the presence of a KIAA1549-BRAF translocation abnormality and an accompanying single nucleotide variant has not been previously described. The detection of this translocation abnormality raises the possibility that the spindle cell tumors in infants with an absence of the ETV6-NTRK3 fusion gene abnormality might have a distinct pathogenetic mechanism different from the previously known IFS and congenital mesoblastic nephroma. Furthermore, the discovery of BRAF translocation and its aberrant signaling of the mitogen-activated protein kinase (MAPK) pathway in this tumor contributes to the promise of clinical benefit of using the MEKi trametinib for the treatment of progressive disease that is refractory to conventional chemotherapy. 

Read Full Article HTML DOI: 10.29328/journal.apcr.1001023 Cite this Article Read Full Article PDF

References

  1. Davis JL, Antonescu CR, Bahrami A. Infantile fibrosarcoma. In WHO classification of tumours: Soft tissue and bone tumours. IARC. 2020;
  2. Antonescu CR. Emerging soft tissue tumors with kinase fusions: An overview of the recent literature with an emphasis on diagnostic criteria. Genes Chromosomes Cancer. 2020; 59: 437–444. PubMed: https://pubmed.ncbi.nlm.nih.gov/32243019/
  3. Robinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES, et al. Integrative genomics viewer. Nat Biotechnol. 2011; 29: 24–26. PubMed: https://pubmed.ncbi.nlm.nih.gov/21221095/
  4. McLeod C, Gout AM, Zhou X, Thrasher A, Rahbarinia D, et al. St. Jude Cloud: A Pediatric Cancer Genomic Data-Sharing Ecosystem. Cancer Discov. 2021; 11: 1082–1099. PubMed: https://pubmed.ncbi.nlm.nih.gov/33408242/
  5. Rankin A, Johnson A, Roos A, Kannan G, Knipstein J, et al. Targetable BRAF and RAF1 Alterations in Advanced Pediatric Cancers. The Oncologist. 2021; 26; e153-e163.PubMed: https://pubmed.ncbi.nlm.nih.gov/32918774/
  6. Kao YC, Fletcher CDM, Alaggio R, Wexler L, Zhang L, et al. Recurrent BRAF Gene Fusions in a Subset of Pediatric Spindle Cell Sarcomas: Expanding the Genetic Spectrum of Tumors With Overlapping Features With Infantile Fibrosarcoma. Am J Surg Pathol. 2018; 42: 28–38. PubMed: https://pubmed.ncbi.nlm.nih.gov/28877062/
  7. Penning AJ, Al-Ibraheemi A, Michal M, Larsen BT, Cho SJ, et al. Novel BRAF gene fusions and activating point mutations in spindle cell sarcomas with histologic overlap with infantile fibrosarcoma. Mod Pathol. 2021; 34: 1530–1540. PubMed: https://pubmed.ncbi.nlm.nih.gov/33850302/
  8. Knezevtch SR, Garnett MJ, Pysher TJ, Beckwith JB, Grundy PE, et al. ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma. Cancer Res. 1998; 58: 5046-5048. PubMed: https://pubmed.ncbi.nlm.nih.gov/9823307/
  9. Wegert J, Vokuhl C, Collord G, Del Castillo Velasco-Herrera M, Farndon SJ, et al. Recurrent intragenic rearrangements of EGFR and BRAF in soft tissue tumors of infants. Nat Commun. 2018; 9: 2378. PubMed: https://pubmed.ncbi.nlm.nih.gov/29915264/
  10. Perreault S, Larouche V, Tabori U, Hawkin C, Lippé S, et al. A phase 2 study of trametinib for patients with pediatric glioma or plexiform neurofibroma with refractory tumor and activation of the MAPK/ERK pathway: TRAM-01. BMC Cancer. 2019; 19: 1250. PubMed: https://pubmed.ncbi.nlm.nih.gov/31881853/
  11. Selt F, van Tilburg CM, Bison B, Sievers P, Harting I, et al. Response to trametinib treatment in progressive pediatric low-grade glioma patients. J Neurooncol. 2020; 149: 499–510. PubMed: https://pubmed.ncbi.nlm.nih.gov/33026636/
  12. Petrilli AM, Fernández-Valle C. Role of Merlin/NF2 inactivation in tumor biology. Oncogene. 2016; 35: 537–548. PubMed: https://pubmed.ncbi.nlm.nih.gov/25893302/

Figures:

Figure 1

Figure 1

Figure 1

Figure 2

Figure 1

Figure 3

Similar Articles

Recently Viewed

Read More

Most Viewed

Read More