FUS-NFATc2 sarcoma of bone, a novel molecular entity with aggressive behavior: Clinical and molecular pathology findings of two cases
Invited conference paper presented and published in conference proceedings



FUS-NFATc2 is a novel fusion gene recently described in rare cases of aggressive primary bone sarcomas with small round cell morphology. Although this fusion shares homology with EWSR1-NFATc2, a recent transcriptomic study demonstrated that they are divergent, as FUS-NFATc2 displays resemblance to the highly aggressive CIC-rearranged sarcoma family. Here, we describe the clinical, pathologic and genomic findings of two cases.

Case 1, from Hong Kong, was molecularly profiled by RNA sequencing using Illumina Pan Cancer RNA kit. Case 2, from Vancouver, was molecularly profiled by whole genome and whole transcriptome sequencing through the local Personalized Oncogenomics consortium project. The results in both cases were confirmed by PCR and Sanger sequencing.

Case 1, a 47 y/o male with a painful enlarging 7.8 cm distal femur mass with soft tissue extension, no metastases at time of diagnosis. Pathology showed a highly proliferative small round blue cell tumor with osteoblastic differentiation by immunostain. RNA-seq showed FUS(exon6)-NFATC2(exon3) fusion. The patient underwent neoadjuvant VAC/IE chemotherapy, with resolution of pain but stable lesional size. Case 2, a 69 y/o male presented with a 9.2 cm distal femur mass with lung metastases. Pathology showed mixed epithelioid and spindled morphology with chondroid and osteoid matrix; a diagnosis of osteosarcoma was made. The patient underwent resection of primary tumor, pseudoneoadjuvant cisplatin/doxorubicin with partial response followed by lung metastatectomy, but developed recurrent subcutaneous metastasis. Whole transcriptome sequencing showed FUS(exon6)-NFATC2(exon3) fusion. The patient did not receive any further chemotherapy due to poor performance status and died of progressive disease at 15 months post diagnosis.

These two cases support the notion of FUS-NFATC2 sarcoma as a distinct molecular entity with aggressive clinical behavior that requires development of a tailored therapeutic approach. The clinical and pathologic overlap with osteosarcomas and other small round cell tumors can lead to diagnostic pitfalls, and justifies comprehensive fusion gene testing of any unusual primary bone sarcomas.
著者M.D. Lacambra, H. Loong, K.F. To, X. Feng, G. Taylor, E. Pleasance, J. Laskin, M. Marra, J. Griffith, H.Y.M. Yeung, K. Wong, C. Chow, S. Kumta, W.H.A. Ng, T. Tse, C. Tong, T. Ng
會議名稱ESMO Asia 2018 Congress
會議論文集題名Annals of Oncology
系列標題Poster display - Cocktail
叢書冊次Pathology/Molecular Biology
期次Suppl 9
出版社Oxford Univ Press Great Clarendon St, Oxford OX2 6DP, England
頁次125 - 125

上次更新時間 2021-11-09 於 23:45