Genomic and transcriptomic characterisation of undifferentiated pleomorphic sarcoma of bone
Articolo
Data di Pubblicazione:
2019
Citazione:
Genomic and transcriptomic characterisation of undifferentiated pleomorphic sarcoma of bone / N. M Ali, S. Niada, A.T. Brini, M. R Morris, S. Kurusamy, A. Alholle, D. Huen, C. R Antonescu, F. Tirode, V. Sumathi, F. Latif. - In: JOURNAL OF PATHOLOGY. - ISSN 0022-3417. - 247:2(2019 Feb), pp. 166-176. [10.1002/path.5176]
Abstract:
Undifferentiated pleomorphic sarcoma of bone (UPSb) is a rare primary bone sarcoma that lacks a specific line of differentiation. There is very little information about the genetic alterations leading to tumourigenesis or malignant
transformation. Distinguishing between UPSb and other malignant bone sarcomas, including dedifferentiated
chondrosarcoma and osteosarcoma, can be challenging due to overlapping features. To explore the genomic and
transcriptomic landscape of UPSb tumours, whole-exome sequencing (WES) and RNA sequencing (RNA-Seq) were
performed on UPSb tumours. All tumours lacked hotspot mutations in IDH1/2 132 or 172 codons, thereby excluding
the diagnosis of dedifferentiated chondrosarcoma. Recurrent somatic mutations in TP53 were identified in four of
14 samples (29%). Moreover, recurrent mutations in histone chromatin remodelling genes, including H3F3A, ATRX
and DOT1L, were identified in five of 14 samples (36%), highlighting the potential role of deregulated chromatin
remodelling pathways in UPSb tumourigenesis. The majority of recurrent mutations in chromatin remodelling
genes identified here are reported in COSMIC, including the H3F3A G34 and K36 hotspot residues. Copy number
alteration analysis identified gains and losses in genes that have been previously altered in UPSb or UPS of soft
tissue. Eight somatic gene fusions were identified by RNA-Seq, two of which, CLTC-VMP1 and FARP1-STK24, were
reported previously in multiple cancers. Five gene fusions were genomically characterised. Hierarchical clustering
analysis, using RNA-Seq data, distinctly clustered UPSb tumours from osteosarcoma and other sarcomas, thus
molecularly distinguishing UPSb from other sarcomas. RNA-Seq expression profiling analysis and quantitative
reverse transcription-polymerase chain reaction showed an elevated expression in FGF23, which can be a potential
molecular biomarker for UPSb. To our knowledge, this study represents the first comprehensive WES and RNA-Seq
analysis of UPSb tumours revealing novel protein-coding recurrent gene mutations, gene fusions and identifying
a potential UPSb molecular biomarker, thereby broadening the understanding of the pathogenic mechanisms and
highlighting the possibility of developing novel targeted therapeutics.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Undifferentiated pleomorphic sarcoma of bone; UPSb
Elenco autori:
N. M Ali, S. Niada, A.T.M. Brini, M. R Morris, S. Kurusamy, A. Alholle, D. Huen, C. R Antonescu, F. Tirode, V. Sumathi, F. Latif
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