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
2831 - Interleukin-6 as a Predictive Marker for Early Response to Induction Chemotherapy in Acute Myeloblastic Leukaemia
Presenter: Salah Khallaf
Session: Poster Display session 1
Resources:
Abstract
6014 - Impact of FLT3-ITD mutation on post-transplant outcome of adult AML is modified by the concomitant NPM1 mutation and pre-transplant remission status: A report from Taiwan Bone Marrow Transplant Registry (TBMTR)
Presenter: Su-peng Yeh
Session: Poster Display session 1
Resources:
Abstract
2914 - Efficacy endpoints studied in clinical trials for early-onset leukaemia
Presenter: Dylan Said
Session: Poster Display session 1
Resources:
Abstract
4691 - High triglyceride is a major risk factor of DIC and differentiation syndrome in acute promyelocytic leukemia
Presenter: Tomohiro Yamakawa
Session: Poster Display session 1
Resources:
Abstract
4395 - DREAMM 4: A Phase I/II single-arm open-label study to explore safety and clinical activity of belantamab mafodotin (GSK2857916) administered in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma (RRMM)
Presenter: Suzanne Trudel
Session: Poster Display session 1
Resources:
Abstract
2808 - A Phase 1 Study of HMPL-523, a Selective Oral Anti-Spleen Tyrosine Kinase Inhibitor, in Patients with Relapsed or Refractory Lymphoma
Presenter: Nathan Fowler
Session: Poster Display session 1
Resources:
Abstract
4403 - A Phase 1 Study of HMPL-689, a Selective Oral Phosphoinositide 3-Kinase-Delta Inhibitor, in Patients with Relapsed or Refractory Lymphoma
Presenter: Jonathon Cohen
Session: Poster Display session 1
Resources:
Abstract
3357 - A global patient-driven Facebook study in a very rare sarcoma: Health-related quality of life in Epithelioid Hemangioendothelioma (EHE) patients
Presenter: Marije Weidema
Session: Poster Display session 1
Resources:
Abstract
2475 - Qualitative study of patients’ experiences of living with and beyond a soft tissue sarcoma diagnosis: the impact of sarcoma specialist services
Presenter: Ana Martins
Session: Poster Display session 1
Resources:
Abstract
2640 - Health-related quality of life issues of patients affected by desmoid-type fibromatosis; experiences from two countries
Presenter: Milea Timbergen
Session: Poster Display session 1
Resources:
Abstract