TY - JOUR
T1 - Novel NTRK3 Fusions in Fibrosarcomas of Adults
AU - Yamazaki, Fumito
AU - Nakatani, Fumihiko
AU - Asano, Naofumi
AU - Wakai, Susumu
AU - Sekimizu, Masaya
AU - Mitani, Sachiyo
AU - Kubo, Takashi
AU - Kawai, Akira
AU - Ichikawa, Hitoshi
AU - Yoshida, Akihiko
N1 - Funding Information:
This work was supported in part by AMED (17ck0106168h0003), the National Cancer Center Research and Development Fund (29-A-2), and JSPS Grant-in-Aid for Young Scientists (18K15108).
Funding Information:
Conflicts of Interest and Source of Funding: This work was supported in part by AMED (17ck0106168h0003), the National Cancer Center Research and Development Fund (29-A-2), and JSPS Grant-in-Aid for Young Scientists (18K15108). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
Publisher Copyright:
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - NTRK fusions in malignant tumors are therapeutic targets of tyrosine kinase inhibitors. Because they occur only in a small subset of mesenchymal tumors, knowledge regarding the corresponding histology is important to effectively identify patients who could benefit from targeted therapy. In this study, using RNA sequencing, we identified novel NTRK3 fusions involving related partner genes in 2 adult bone and soft tissue tumors that met the current histologic criteria of fibrosarcoma. Case 1 involved the left radius of a 38-year-old woman, whereas in case 2, the right thigh of a 26-year-old man was affected. Histologically, both tumors consisted of the long fascicular growth of long spindle cells. The tumor in case 1 additionally showed focal myxoid changes. Tumor cells had nonpleomorphic, atypical nuclei, and lacked evidence of a specific line of differentiation. Both tumors showed widespread CD34 immunoreactivity and very limited expression of actin. RNA sequencing detected in-frame fusion transcripts of STRN (exon 3)-NTRK3 (exon 14) in case 1 and STRN3 (exon 3)-NTRK3 (exon 14) in case 2, which were confirmed by reverse transcription polymerase chain reaction and Sanger sequencing. Pan-TRK immunostaining was diffusely positive in both cases. Fluorescence in situ hybridization showed signal patterns compatible with NTRK3 rearrangements in both cases, with case 2 additionally harboring a CDKN2A homozygous deletion. This study expands the clinicopathologic and genetic spectrum of sarcomas associated with NTRK fusions, and suggests that CD34-positive fibrosarcoma of bone and soft tissue could be a good candidate for NTRK testing.
AB - NTRK fusions in malignant tumors are therapeutic targets of tyrosine kinase inhibitors. Because they occur only in a small subset of mesenchymal tumors, knowledge regarding the corresponding histology is important to effectively identify patients who could benefit from targeted therapy. In this study, using RNA sequencing, we identified novel NTRK3 fusions involving related partner genes in 2 adult bone and soft tissue tumors that met the current histologic criteria of fibrosarcoma. Case 1 involved the left radius of a 38-year-old woman, whereas in case 2, the right thigh of a 26-year-old man was affected. Histologically, both tumors consisted of the long fascicular growth of long spindle cells. The tumor in case 1 additionally showed focal myxoid changes. Tumor cells had nonpleomorphic, atypical nuclei, and lacked evidence of a specific line of differentiation. Both tumors showed widespread CD34 immunoreactivity and very limited expression of actin. RNA sequencing detected in-frame fusion transcripts of STRN (exon 3)-NTRK3 (exon 14) in case 1 and STRN3 (exon 3)-NTRK3 (exon 14) in case 2, which were confirmed by reverse transcription polymerase chain reaction and Sanger sequencing. Pan-TRK immunostaining was diffusely positive in both cases. Fluorescence in situ hybridization showed signal patterns compatible with NTRK3 rearrangements in both cases, with case 2 additionally harboring a CDKN2A homozygous deletion. This study expands the clinicopathologic and genetic spectrum of sarcomas associated with NTRK fusions, and suggests that CD34-positive fibrosarcoma of bone and soft tissue could be a good candidate for NTRK testing.
KW - NTRK3
KW - adult
KW - fibrosarcoma
KW - gene fusion
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U2 - 10.1097/PAS.0000000000001194
DO - 10.1097/PAS.0000000000001194
M3 - Article
C2 - 30520818
AN - SCOPUS:85058161236
VL - 43
SP - 523
EP - 530
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
SN - 0147-5185
IS - 4
ER -