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

Alessio Valletti, Anna Anselmo, Marina Mangiulli, Ilenia Boria, Flavio Mignone, Giuseppe Merla, Vincenzo D'Angelo, Apollonia Tullo, Elisabetta Sbisà, Anna M. D'Erchia, Graziano Pesole

Research output: Contribution to journalArticle

Abstract

Background: Many 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.Results: We 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.Conclusion: This 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.

Original languageEnglish
Article number230
JournalMolecular Cancer
Volume9
DOIs
Publication statusPublished - Sep 2 2010

Fingerprint

Expressed Sequence Tags
Exons
Alternative Splicing
Glioblastoma
Tumor Biomarkers
Neoplasms
Neoplasm Genes
Computer Simulation
Nervous System
Genes
Biomarkers
Genome
Databases
Messenger RNA
Proteins
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

Cite this

Identification of tumor-associated cassette exons in human cancer through EST-based computational prediction and experimental validation. / Valletti, Alessio; Anselmo, Anna; Mangiulli, Marina; Boria, Ilenia; Mignone, Flavio; Merla, Giuseppe; D'Angelo, Vincenzo; Tullo, Apollonia; Sbisà, Elisabetta; D'Erchia, Anna M.; Pesole, Graziano.

In: Molecular Cancer, Vol. 9, 230, 02.09.2010.

Research output: Contribution to journalArticle

Valletti, A, Anselmo, A, Mangiulli, M, Boria, I, Mignone, F, Merla, G, D'Angelo, V, Tullo, A, Sbisà, E, D'Erchia, AM & Pesole, G 2010, 'Identification of tumor-associated cassette exons in human cancer through EST-based computational prediction and experimental validation', Molecular Cancer, vol. 9, 230. https://doi.org/10.1186/1476-4598-9-230
Valletti, Alessio ; Anselmo, Anna ; Mangiulli, Marina ; Boria, Ilenia ; Mignone, Flavio ; Merla, Giuseppe ; D'Angelo, Vincenzo ; Tullo, Apollonia ; Sbisà, Elisabetta ; D'Erchia, Anna M. ; Pesole, Graziano. / Identification of tumor-associated cassette exons in human cancer through EST-based computational prediction and experimental validation. In: Molecular Cancer. 2010 ; Vol. 9.
@article{a5259766be5849a7b2573794fb10975b,
title = "Identification of tumor-associated cassette exons in human cancer through EST-based computational prediction and experimental validation",
abstract = "Background: Many 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.Results: We 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.Conclusion: This 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.",
author = "Alessio Valletti and Anna Anselmo and Marina Mangiulli and Ilenia Boria and Flavio Mignone and Giuseppe Merla and Vincenzo D'Angelo and Apollonia Tullo and Elisabetta Sbis{\`a} and D'Erchia, {Anna M.} and Graziano Pesole",
year = "2010",
month = "9",
day = "2",
doi = "10.1186/1476-4598-9-230",
language = "English",
volume = "9",
journal = "Molecular Cancer",
issn = "1476-4598",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Identification of tumor-associated cassette exons in human cancer through EST-based computational prediction and experimental validation

AU - Valletti, Alessio

AU - Anselmo, Anna

AU - Mangiulli, Marina

AU - Boria, Ilenia

AU - Mignone, Flavio

AU - Merla, Giuseppe

AU - D'Angelo, Vincenzo

AU - Tullo, Apollonia

AU - Sbisà, Elisabetta

AU - D'Erchia, Anna M.

AU - Pesole, Graziano

PY - 2010/9/2

Y1 - 2010/9/2

N2 - Background: Many 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.Results: We 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.Conclusion: This 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.

AB - Background: Many 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.Results: We 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.Conclusion: This 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.

UR - http://www.scopus.com/inward/record.url?scp=77956492769&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956492769&partnerID=8YFLogxK

U2 - 10.1186/1476-4598-9-230

DO - 10.1186/1476-4598-9-230

M3 - Article

C2 - 20813049

AN - SCOPUS:77956492769

VL - 9

JO - Molecular Cancer

JF - Molecular Cancer

SN - 1476-4598

M1 - 230

ER -