Wednesday, 8th March, 2017, 12:00 - 13.00

Characterization of RNA processing alterations in small cell lung cancer

Small cell lung cancer (SCLC) accounts for 15% of all lung cancers. Previous studies have shown high frequency of mutations in TP53 and RB1, and amplification of MYC. However, no targeted therapies have been approved for use in treatment of SCLC, contrary to other lung cancer types like adenocarcinoma. Accordingly, chemotherapy remains the only treatment, which is initially effective but is inexorably followed by rapid relapse in the majority of the patients.

Understanding the molecular mechanisms underneath this disease is thus necessary for improving treatment. We have analyzed RNA-seq from 73 RNA-seq SCLC patient samples from and characterized the transcriptomic changes between tumor and normal tissues. We have validated these changes on other 2 cohorts of 31 and 19 RNA-seq SCLC patient samples. In order to identify those changes specific of SCLC, and to account for the fact that SCLC tumors have different cell type of origin than other lung tumors, we performed comparisons against more than 1000 non-small cell lung samples from The Cancer Genome Atlas and against neuroendocrine lung carcinoid tumors.

Additionally, using 71 WGS SCLC samples, we looked for somatic mutations disrupting intronic and exonic splicing regulatory motifs that could be responsible for these changes in the transcriptome. This is the largest analysis performed to date of RNA processing alterations and associated mutations in SCLC, which could lead to the uncovering of novel targets of therapy.

Speaker: Juan Luís Trincado, Computational RNA Biology, GRIB (IMIM/UPF)

Room Aula 473.10 (PRBB, 4th floor)