IndraLab

Statements


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sparser
"This suggests that promoter activity of the FN1 gene conferred increased FN1-ACVR2A transcript in the tumor."

sparser
"RNA sequencing further revealed that expression of the ACVR2A gene increased more than 25-fold in the FN1-ACVR2A fusion-positive case (CS6T) compared with that of other samples (CS1T and CS7T) (Supplemental Table S10)."

sparser
"However, analysis of a synovial subtype identified recurrent FN1-ACVR2A fusion transcript, which further suggests a molecular link between chondrosarcoma and osteochondromatosis."

sparser
"Aberrant FN1-ACVR2A gene fusion and recurrent ACVR2A mutations also warrant small-molecular inhibitors targeting activin receptor kinases ( xref ) as potential therapeutic modalities against a subset of chondrosarcoma."

sparser
"The presence of a FN1-ACVR2 fusion did not distinguish between benign and malignant disease, but we showed that copy number alteration of CDKN2A appears to be a valuable predictor of malignancy, similarly to conventional cartilaginous tumours ( xref , xref ) where copy number alterations of CDKN2A appear exclusively in chondrosarcomas."

sparser
"Remarkably we found no difference in the histological appearance between synovial chondromatosis with and without FN1-ACVR2A rearrangements."

sparser
"FN1-ACVR2A gene fusions have been recently identified in synovial chondromatosis. xref , xref It was first reported by Totoki et al. xref who investigated chondrosarcomas by whole genome sequencing and found a single case of synovial chondrosarcoma with an FN1 - ACVR2A gene fusion."

sparser
"Four additional cases were tested by whole transcriptome sequencing, showing an FN1-ACVR2A transcript in all cases, including 3 synovial chondromatosis and 1 synovial chondrosarcoma."

sparser
"Moreover, our results showed that 56% (15 of 27) of the cases were positive for FN1-ACVR2A fusion, significantly higher than the 19% reported by Amary et al. None of the cases in our study showed only ACVR2A gene rearrangement with no FN1 gene rearrangement."

sparser
"However, it is not possible to state which of these structurally altered genes drives tumour progression as both FN1-ACVR2A and ACVR2A-FN1 are predicted to be in-frame."

sparser
"This same mechanism may explain the action of the FN1-ACVR2A fusion, namely that FN1 may facilitate dimerisation of ACVR2A inducing activin signaling."

sparser
"The true prevalence of cases harbouring these alterations is likely to be higher on the basis that only one of three synovial chondroma/chondromatosis cases that revealed a FN1-ACVR2A fusion gene by RNA sequencing demonstrated break-apart signals involving both genes."

sparser
"The high incidence of FN1-ACVR2A gene fusions in synovial osteochondromatosis is reported [ xref , xref ]."

sparser
"Furthermore, a novel FN1-ACVR2A fusion transcript was observed in both chondrosarcoma and osteochondromatosis cases."

sparser
"Among these, two ( ACVR2A-FN1 and FN1-ACVR2A ) were expressed and validated in the synovial CS6T case ( xref ; Supplemental Fig. S11)."

sparser
"K36M) ( xref ), mesenchymal chondrosarcoma is characterized by the fusion of HEY1-NCOA2 ( xref ), chondromyxoid fibroma is characterized by GRM1 rearrangements ( xref ), aneurysmal bone cyst is characterized by USP6 rearrangements ( xref ), osteoblastoma/osteoid osteoma is characterized by FOS/FOSB rearrangements ( xref ), and synovial chondromatosis is characterized by the fusion of FN1-ACVR2A and ACVR2A-FN1 ( xref )."

sparser
"Both these entities are characterized by FN1-ACVR2A and ACVR2A-FN1 fusions [ xref ], which are present in at least 50% of synovial chondromatosis."

sparser
"To analyse further and validate the findings, we performed FISH and demonstrated recurrent FN1-ACVR2A rearrangements in synovial chondromatosis (57%), and chondrosarcoma secondary to synovial chondromatosis (75%), showing that FN1 and/or AVCRA2 gene rearrangements do not distinguish between benign and malignant synovial chondromatosis."

sparser
"RNA sequencing revealed the presence of the FN1-ACVR2A fusion in several cases that were negative by FISH suggesting that the true prevalence of this fusion is potentially higher than 57%."

sparser
"The recent findings of FN1-ACVR2A and ACVR2A-FN1 in-frame fusions in a case of chondrosarcoma arising secondary to synovial chondromatosis and in one of seven cases of synovial chondromatosis ( xref ), indicate that these lesions represent neoplasms, and that they rarely transform into secondary chondrosarcoma ( xref – xref )."

sparser
"Results showed that FN1 and /or ACVR2A gene rearrangements were noted in 18 cases (67%), with an FN1-ACVR2A fusion being confirmed in 15 (56%) cases."

sparser
"Studies using cell proliferation assays have differed on the extent of DNA aneuploidy seen in synovial chondromatosis. xref , xref An FN1-ACVR2A in-frame gene fusion was initially identified in one case each of synovial osteochondromatosis and synovial chondrosarcoma, during a genomic investigation of various benign and malignant cartilaginous neoplasms. xref In a more recent study, Amary et al. further confirmed these findings using FISH analysis and whole-transcriptome RNA sequencing on a large number of cases, showing that 57% of synovial chondromatosis harbored FN1 and/or ACVR2A gene rearrangements. xref Of the 7 synovial chondrosarcomas included in their study, only 4 were informative by FISH, showing evidence of FN1 and/or the ACVR2A gene rearrangements in 3 cases. xref "

sparser
"In this study we investigate a large cohort of synovial chondromatosis for the prevalence of the FN1-ACVR2A fusion."

sparser
"As this lesion harbored a previously unreported gene fusion, we attempted to establish its recurrent potential vis-à-vis the more common FN1-ACVR2A fusion."

sparser
"FN1-ACVR2A gene fusion seen in 67% of synovial chondromatosis."