Thursday, 9th March, 2017, 12:00
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
Room Aula room 473.10 (PRBB, 4th floor)
Thursday, 15th December, 2016, 12:00
Population heterogeneity within tumors is essential to the development of drug resistance. However, precise quantification of cellularity levels of subpopulations, and in particular how they evolve in response to treatment, has been challenging. Here we describe the high precision characterization of subclonal evolution within triple-negative breast cancer patient-derived xenografts (PDXs) generated from three patients in response to multiple chemotherapies, covering >100 total samples and allowing for extensive intratumoral comparisons. Computational mutation and copy number analysis from post-treatment sequencing indicated sample-specific differences in tumor populations both in response to treatment and due to genetic drift. I will describe the evolutionary behaviors we have observed, which include selective sweeps, spatial diffusion, and symbiosis.
Speaker: Jeffrey Chuang, Ph.D, The Jackson Laboratory for Genomic Medicine; University of Connecticut Health Center Dept. of Genetics and Genome Sciences; Host: Eduardo Eyras
Room Aula room 473.10 (4th floor)
Thursday, 28th April, 2016, 12:00
In our lab we study alterations in splicing in multiple cancer types. These splicing alterations occur through somatic mutations in cis in introns and exons or through other mechanisms in trans. We recently published the largest analysis to date of the splicing alterations in cancer (Sebestyen et al. 2016) that includes an exhaustive analysis of the mutations, copy number variations and expression changes in RNA binding proteins and how these impact alternative splicing in multiple cancer. Our previous work lead us to some open ended question about mutations that affect splicing in cis. Therefore, currently we are developing a method for identifying and characterizing significantly mutated regions (SMRs) inside genes from whole genome sequencing (WGS) data and their impact on RNA processing in multiple tumors. I will be presenting some preliminary results about this project.
Speaker: Babita Singh - Computational Genomics group of GRIB (IMIM-UPF)
Room Aula room 473.10 (4th floor)
Thursday, 8th October, 2015, 12:00
Small non-coding RNAs play a vital role in several cellular processes. Their pattern of processing and its traces in short RNA-Seq reads data is a powerful and unbiased resource that can be used to study those important molecules. Here we present a collection of software tools based on the analysis of processing patterns for the discovery, annotation and characterization of small non-coding RNAs.
Speaker: AMADIS PAGÉS - Computational Genomics, GRIB
Room Marie Curie Room (Ground floor)
Thursday, 16th April, 2015, 11:00h
Alterations in RNA processing are emerging as important signatures to understand tumor formation and to develop new therapeutic strategies. However, it is not yet known the extent to which these alterations can be considered drivers or whether specific patterns of RNA processing can be predictive of prognosis. We describe our efforts to determine the functional impact and relevance in cancer of RNA processing alterations measured in 11 cancer types. We describe multiple alterations in RNA regulatory proteins and their target genes, and investigate RNA alterations that are predictive of tumor stage and survival. These novel signatures expand the catalogue of candidate actionable alterations in tumors and potentially complement current strategies in precision cancer medicine.
Speaker: EDUARDO EYRAS Computational Genomics Group - GRIB
Room Aula room (4th floor)
Thursday, 20th November, 2014, 11:00-12:00
Speaker: Ivan Dotu; Biology Department, Boston College.
Room Aula room (470.03 – 4th floor)
Thursday, 8th May, 2014, 11:00
Both chromatin state and binding of splicing factors to regulatory sequence elements of pre-mRNA have been shown to affect alternative splicing outcomes. Yet the precise interplay between these two determinants is not known. The availability of a relatively large number of relevant, publicly available, high-throughput ChIP-seq, CLIP-seq, and RNA-seq datasets make it possible to study this in depth on a genome-wide scale. Read profiling is a commonly used method to increase the signal strength of high-throughput data by combining reads from a set of similar loci rather than examining each locus individually, thus increasing the signal and statistical power. However, profiles often convey only qualitative information, In this talk I will present a method we have developed to calculate exact P-values for comparison of a profile with a proper control. The method allows for single-nucleotide resolution in principle, and can be used on most types of high-throughput sequenceing data. I will also show how we have applied the method thus far to study the relationship between chromatin and splicing factors.
Speaker: Isaac J. Kremsky Computational Genomics group, GRIB
Thursday, 13th February, 2014, 11:00
Speaker: Endre Sebestyén - Computational Genomics, GRIB (IMIM-UPF)
Room Sala 473.10
Thursday, 28th November, 2013, 11:00
Current cancer genomics projects apply high-throughput technologies to discover recurrent genetic variations in patient samples. These efforts are crucial to describe the genetic diversity of cancer and to classify into novel subtypes for improved prognosis and therapeutics. These genome-scale studies focus mostly on the detection of alterations of the DNA and the expression of genes. However, alterations in Alternative Splicing (AS), which hold important signatures that can provide novel prognostic and therapeutical strategies, have not been yet thoroughly characterized. We have used RNA sequencing data from The Cancer Genome Atlas (TCGA) project for hundreds of tumor samples and paired normal tissues to study the splicing changes and differential expression of Splicing Factors (SFs) and RNA binding proteins (RBPs) in 13 different cancer types. We find new proteins and splicing events that are recurrently altered in tumors. Additionally, by using correlations, we detect possible association of RBPs and events, suggesting splicing regulatory modules. Our analysis indicates that different cancers present similar alterations, suggesting a general path for cells towards cancer by concurrent splicing alterations. This analysis provides useful information to elucidate the impact of alternative splicing in the functional dynamics of cell transformation in multiple cancer types and may help uncovering novel therapeutic strategies.
Speaker: Eduardo Eyras - Computacional Genomics group of GRIB (IMIM - UPF)
Room Aula (473.10)
Thursday, 9th February, 2012, 11:00
Speaker: Endre Sebestyen. Regulatory Genomics Group- GRIB