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
YO10 - Rectal Follicular Dendritic Cell Sarcoma
Presenter: Kripa Bajaj
Session: Poster display session
Resources:
Abstract
YO11 - Postoperative metastasis prediction based on portal vein circulating tumor cells detected by flow cytometry in periampullary or pancreatic cancer
Presenter: Lianyuan Tao
Session: Poster display session
Resources:
Abstract
YO12 - Case report of Hepatic EBV-associated smooth muscle tumor in AIDS patient
Presenter: Gorawich Kerkarchachai
Session: Poster display session
Resources:
Abstract
YO13 - IgG4-related pseudo-tumor of the kidney and multiple organ involvement mimicked malignancy
Presenter: Wasamol Mahaparn
Session: Poster display session
Resources:
Abstract
YO14 - Urachal Adenocarcinoma: Case Report
Presenter: Michelle Joane Alcantara
Session: Poster display session
Resources:
Abstract
YO15 - Concurrent Atezolizumab-Radiotherapy in Locally Recurrent Urinary Bladder Carcinoma: A Case Report
Presenter: Ma. Angelle Lalaine Dantes
Session: Poster display session
Resources:
Abstract
YO16 - Clear cell RCC with synchronous metastasis at transplanted kidney and bone in patient post Cadaveric donor kidney transplantation
Presenter: Punyaporn Cheewasathianchai
Session: Poster display session
Resources:
Abstract
YO17 - Serous ovarian cancer treated with palbociclib and letrozole
Presenter: Dai Wee Lee
Session: Poster display session
Resources:
Abstract
YO18 - A patient with Peutz-Jegher syndrome who incidentally found sex cord stromal tumor: a case report
Presenter: Pongput Pimsa
Session: Poster display session
Resources:
Abstract
YO19 - A case of CLL/SLL with transdifferentiation to dendritic cell tumor and possibly a hybrid lymphodendritic cell neoplasm:The missing link?
Presenter: Yanping Chen
Session: Poster display session
Resources:
Abstract