Identification of tumor-associated cassette exons in human cancer through EST-based computational prediction and experimental validation

Molecular Cancer

Research

Ilenia Boria¹  Alessio Valletti¹  Marina Mangiulli¹  Anna Maria D'Erchia¹  Graziano Pesole²  Flavio Mignone³  Vincenzo D'Angelo⁴  Anna Anselmo⁵  Elisabetta Sbisà⁶  Apollonia Tullo⁶  Giuseppe Merla⁷ 

[1] Dipartimento di Biochimica e Biologia Molecolare "E. Quagliariello", University of Bari, via Orabona, 4, 70126, Bari, Italy;Dipartimento di Biochimica e Biologia Molecolare "E. Quagliariello", University of Bari, via Orabona, 4, 70126, Bari, Italy;Istituto Biomembrane e Bioenergetica del Consiglio Nazionale delle Ricerche, via Amendola 165/A, 70126, Bari, Italy;Dipartimento di Chimica strutturale e Stereochimica Inorganica, University of Milan, via Venezian, 12, 20133, Milan, Italy;Dipartimento di Neuroscienze, Divisione di Neurochirurgia, IRCCS Casa Sollievo della Sofferenza, 71013, San Giovanni Rotondo, Italy;Dipartimento di Scienze Biomolecolari e Biotecnologie, University of Milan, via Celoria 26, 20133, Milan, Italy;Istituto Tecnologie Biomediche del Consiglio Nazionale delle Ricerche, sede di Bari, via Amendola 122/D, 70126, Bari, Italy;Laboratorio di Genetica Medica, IRCCS Casa Sollievo della Sofferenza, 71013, San Giovanni Rotondo, Italy;

关键词: Alternative Splice;    Splice Site;    Splice Event;    Alternative Transcript;    Significant Differential Expression;   

DOI  :  10.1186/1476-4598-9-230

 received in 2010-06-09, accepted in 2010-09-02,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundMany evidences report that alternative splicing, the mechanism which produces mRNAs and proteins with different structures and functions from the same gene, is altered in cancer cells. Thus, the identification and characterization of cancer-specific splice variants may give large impulse to the discovery of novel diagnostic and prognostic tumour biomarkers, as well as of new targets for more selective and effective therapies.ResultsWe present here a genome-wide analysis of the alternative splicing pattern of human genes through a computational analysis of normal and cancer-specific ESTs from seventeen anatomical groups, using data available in AspicDB, a database resource for the analysis of alternative splicing in human. By using a statistical methodology, normal and cancer-specific genes, splice sites and cassette exons were predicted in silico. The condition association of some of the novel normal/tumoral cassette exons was experimentally verified by RT-qPCR assays in the same anatomical system where they were predicted. Remarkably, the presence in vivo of the predicted alternative transcripts, specific for the nervous system, was confirmed in patients affected by glioblastoma.ConclusionThis study presents a novel computational methodology for the identification of tumor-associated transcript variants to be used as cancer molecular biomarkers, provides its experimental validation, and reports specific biomarkers for glioblastoma.

【 授权许可】

Unknown   
© Valletti et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.