Abstract 409P
Background
L-type sarcoma (liposarcoma + leiomyosarcoma) is the most common subtype of soft tissue sarcoma (STS). Leiomyosarcoma (LMS) and dedifferentiated LPS (DDLPS) are more aggressive with worse outcomes than well-differentiated sarcoma. Efforts have thus been made to decipher the difference of oncogenesis between DDLPS and LMS, and assist in the choice of treatment.
Methods
WES was conducted on 32 STS (20 LMS and 12 DDLPS) and matched peripheral blood. Somatic SNVs and indels were identified by GATK tools. Recurrent somatic copy-number alterations (SCNA) were called using Control-FREEC and GISTIC2.0. We further conducted RNA-Seq on 8 DDLPS samples and 8 LMS samples, and use STAR-Fusion to reveal the distinct chromosome rearrangement patterns of LMS and DDLPS samples.
Results
We identified top 20 highly variable genes between LMS and DDLPS. 55% LMS (n = 11) carry deletions or mutations of TP53. All DDLPS carry wildtype TP53, but chromosome 12q14–15 region which encodes MDM2, CDK4 and HMGA2 are highly amplified in all DDLPS samples, suggesting distinct mechanisms of TP53 pathway inactivation. Hippo pathway is reported to be involved in resistance to cytotoxic drugs and modulate tumour immunogenicity. In our study, 70% LMS (n = 14) and 58% DDLPS (n = 7) carry at least one Hippo pathway alterations, top variable genes in LMS include DCHS1, LLGL1, AJUBA et al. Among 8 LMS and 8 DDLPS who underwent RNA-Seq, we identified 4 fusion transcripts in 3 LMS and 36 fusion transcripts in 8 DDLPS (P = 0.007). Fusion transcripts involving chromosome 12 (Chr12) are only identified in DDLPS, including 10 interchromosomal and 12 intrachromosomal rearrangements. MDM2 and RAB3IP are the most common fusion partners. There was also significant correlation between MDM2/CDK4 co-amplification and Chr12 rearrangement (P < 0.001). All DDLPS with MDM2/CDK4 co-amplification showed elevated MDM2 and CDK4 co-expression.
Conclusions
LMS and DDPLS carry distinct mutagenic patterns, ranging from SNVs to gross genomic instability. Chromosome rearrangement of DDLPS, particularly in Chr12, result in both gene amplification and fusion events, and these neoantigens produced by gene fusion may open up alternative avenues for immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
YO20 - Can "Superman" have Chronic Myelomonocytic Leukemia?
Presenter: Alexander Luchinin
Session: Poster display session
Resources:
Abstract
YO21 - Sanctuary Site Central Nervous System Relapse-Refractory DLBCL Responding to Nivolumab and Lenalidomide.
Presenter: Irappa Madabhavi
Session: Poster display session
Resources:
Abstract
YO22 - External Auditory Canal Mass: A Case Series of Squamous Cell Carcinoma
Presenter: Mel Valerie Cruz-Ordinario
Session: Poster display session
Resources:
Abstract
YO23 - Soft tissue Giant cell tumor presented as Nasopharyngeal mass: A case report
Presenter: Emmelyn Buenacosa-Nepucpan
Session: Poster display session
Resources:
Abstract
YO25 - Hyperprogression after pembrolizumab in recurrent oropharyngeal cancer and the use of nab-paclitaxel as salvage treatment- A case report.
Presenter: Izzati Rosli
Session: Poster display session
Resources:
Abstract
YO26 - Exacerbation of radiation necrosis around the radiotherapy-pretreated brain metastases site after immune checkpoint inhibitors.
Presenter: Minako Nishio
Session: Poster display session
Resources:
Abstract
YO27 - Comparative Study Of 20Gray/5Fraction And 30Gray/10 Fraction Whole Brain Radiation In Brain Metastasis
Presenter: Pradip Bhandari
Session: Poster display session
Resources:
Abstract
YO28P - The response to anaplastic lymphoma kinase (ALK) inhibitor in metastatic anaplastic thyroid carcinoma (ATC)
Presenter: Nur Faizah Ab Muin
Session: Poster display session
Resources:
Abstract
YO29 - Acute kidney injury secondary to bilateral renal artery tumor thrombosis in a case of posterior mediastinal undifferentiated sarcoma: case report
Presenter: Ritsu Ibusuki
Session: Poster display session
Resources:
Abstract
YO30 - Follicular dendritic cell sarcoma of the tonsil- a multimodality approach
Presenter: Rich Ericson King
Session: Poster display session
Resources:
Abstract