Abstract 3539
Background
Small Cell Lung Cancer (SCLC) is a highly metastatic form of lung cancer and the therapies remain unchanged since 40 years. Therefore, the discovery of novel transcriptomic alterations contributes to develop more effective targeted therapies. Among them, RLF/MYCL1 was described as a recurrent chimera implicated in tumor growth. The non-protein-coding RNA PVT1, linked to MYC expression, and its circular variant circPVT1 are also dysregulated in several malignancies and associated to tumor progression. Nevertheless, their functional and clinical role was only partially explored. We investigated these transcriptomic alterations in SCLC patients and cell lines, aiming at exploring a possible prognostic significance.
Methods
12 SCLC cell lines harboring MYC, MYCN or MYCL1 amplifications were tested by RNA-sequencing and RT-PCR for the recurrence of RLF/MYCL1. Moreover, the relative expression of PVT1/circPVT1 was evaluated by RT-qPCR. To investigate whether these transcriptomic alterations could serve as prognostic markers, overall survival (OS) and progression free survival (PFS) curves were plotted by Kaplan-Meier method according to the recurrence of RLF1/MYCL1 and the PVT1/circPVT1 expression levels in a cohort of 29 SCLC patients.
Results
RNA-seq analysis by ChimeraScan and FusionMap tools identified the occurrence of RLF/MYCL1 in four cell lines, showing the occurrence of two splicing variants originated by the fusion of RLF exon 1 to alternatively MYCL1 exon 2 (longer) or 3 (shorter). The longer variant was also found as recurrent in 16/28 (57.1%) SCLC patients, correlating with a shorter OS (median survival of 11 vs 17 months). Conversely, circPVT1 expression levels, according to the median expression of all SCLC samples, were associated with a better OS (median survival of 14 vs 8 months). No differences were found regarding the DFS and the recurrence of RLF1/MYCL1 or the PVT1/circPVT1 expression levels.
Conclusions
Our results confirmed the recurrence of the RLF/MYCL1 chimera in a high percentage of SCLC samples. Interestingly, our clinical investigations clearly disclosed that both the chimera and circPVT1 could be used as prognostic markers in SCLC, respectively negative and positive, although our results need to be confirmed in a wider cohort of patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
University of Bari, Italy.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4615 - Proteomic Profiling Identifies Molecular Basis of Adverse Event to BPM31510 Exposure: Rationale for Comprehensive Molecular Pharmacodynamics (PD) in Phase 1 Clinical Trial Design
Presenter: Vivek Subbiah
Session: Poster Display session 1
Resources:
Abstract
5052 - Identification of first-in-class, naturally occurring LAG3 checkpoint inhibitor
Presenter: Gennady Bratslavsky
Session: Poster Display session 1
Resources:
Abstract
5336 - Are Epigenetic therapies modifying sensitivity to conventional chemotherapy?
Presenter: Alexandra Bizot
Session: Poster Display session 1
Resources:
Abstract
5739 - Oncogenic mutations at the dimer interface of EGFR lead to formation of covalent homo-dimers and allosteric activation of the kinase domain: A mechanism which alters the selectivity profile of oncogenic EGFR.
Presenter: Elizabeth Buck
Session: Poster Display session 1
Resources:
Abstract
5492 - Basic selective estrogen receptor degraders (B-SERDs) in combination with novel BET inhibitors in ER+ breast cancer
Presenter: Rui Xiong
Session: Poster Display session 1
Resources:
Abstract
5965 - EPI-7386 is a novel N-terminal domain androgen receptor inhibitor for the treatment of prostate cancer
Presenter: Ronan Le Moigne
Session: Poster Display session 1
Resources:
Abstract
3582 - AVID200 neutralizes TGF-beta1 and -beta3, the principal immunosuppressive TGF-beta isoforms overexpressed by tumors, and sensitizes tumors to immune checkpoint inhibitors.
Presenter: Tina Gruosso
Session: Poster Display session 1
Resources:
Abstract
1996 - High NAMPT expression and anti-tumor activity of NAMPT inhibitor in adult T-cell leukemia/lymphoma
Presenter: Tomohiro Kozako
Session: Poster Display session 1
Resources:
Abstract
4307 - TPX-0046 is a novel and potent RET/SRC inhibitor for RET-driven cancers
Presenter: Alexander Drilon
Session: Poster Display session 1
Resources:
Abstract
4869 - In Vivo Evaluation of Cisplatin-loaded PEG-PCL Block Copolymeric Nanoparticles for Anticancer Drug Delivery
Presenter: Yingtzu Yen
Session: Poster Display session 1
Resources:
Abstract