Large-scale Transcriptome Analyses Reveal New Genetic Marker Candidates of Head, Neck, and Thyroid Cancer

Departamento de Bioquímica, Faculdade de Medicina, Universidade de São Paulo, Brazil.
Cancer Research (Impact Factor: 9.33). 04/2005; 65(5):1693-9. DOI: 10.1158/0008-5472.CAN-04-3506
Source: PubMed


A detailed genome mapping analysis of 213,636 expressed sequence tags (EST) derived from nontumor and tumor tissues of the oral cavity, larynx, pharynx, and thyroid was done. Transcripts matching known human genes were identified; potential new splice variants were flagged and subjected to manual curation, pointing to 788 putatively new alternative splicing isoforms, the majority (75%) being insertion events. A subset of 34 new splicing isoforms (5% of 788 events) was selected and 23 (68%) were confirmed by reverse transcription-PCR and DNA sequencing. Putative new genes were revealed, including six transcripts mapped to well-studied chromosomes such as 22, as well as transcripts that mapped to 253 intergenic regions. In addition, 2,251 noncoding intronic RNAs, eventually involved in transcriptional regulation, were found. A set of 250 candidate markers for loss of heterozygosis or gene amplification was selected by identifying transcripts that mapped to genomic regions previously known to be frequently amplified or deleted in head, neck, and thyroid tumors. Three of these markers were evaluated by quantitative reverse transcription-PCR in an independent set of individual samples. Along with detailed clinical data about tumor origin, the information reported here is now publicly available on a dedicated Web site as a resource for further biological investigation. This first in silico reconstruction of the head, neck, and thyroid transcriptomes points to a wealth of new candidate markers that can be used for future studies on the molecular basis of these tumors. Similar analysis is warranted for a number of other tumors for which large EST data sets are available.

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Available from: José Rodrigo Pandolfi
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    • "They described 2,251 unspliced intronic lncRNAs expressed in head and neck tumors and being involved in transcriptional regulation. [23] In the current study, microarray techniques were used to compare the expression profiles of laryngeal cancer tissues and paired normal tissues; this is the first study to provide a complete lncRNA expression profile for LSCC. In total, more than 1400 lncRNAs were found to be differentially expressed by more than two-fold (P<0.05) between cancer tissues and normal tissues. "
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    • "Our group has previously shown that most (at least 74%) annotated protein-coding gene loci generate intragenic lncRNAs that map to intronic regions [26]. Possible relevance of intronic lncRNAs to neoplastic processes was proposed following the observation that subsets of these transcripts are present in gene expression signatures correlated to the degree of malignancy in prostate cancer [17] or to tissue histology in head and neck tumors [27] and renal cell carcinoma [28]. In addition, a number of intronic lncRNAs were found to be regulated by androgen stimulation of cultured prostate cancer cells [29], indicating that these transcripts are expressed in a regulated manner and thus, corroborating the idea that intronic lncRNAs are biologically relevant. "
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    • "An additional problem will be the possibility to distinguish between closely related genes in the basis of partial sequences. EST profiling have been used for the identification of reference genes for quantitative RT-PCR normalization in wheat [26] and barley [27], expression profiling of storage-protein gene families in wheat [28], identification of differentially expressed transcripts from sugarcane maturing stem [29], or the identification of cancer gene-markers in humans [30]. The application of EST profiling to maize TEs is particularly appropriate. "
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