Quantitative real-time PCR identifies a critical region of deletion on 22q13 related to prognosis in oral cancer

Reis, Patrícia P.; Rogatto, Sílvia Regina; Kowalski, Luiz Paulo; Nishimoto, Inês Nobuko; Montovani, Jair Cortez; Corpus, George; Squire, Jeremy A.; Kamel‐Reid, Suzanne

doi:10.1038/sj.onc.1205864

Cited by 44 publications

(25 citation statements)

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“…Comparative genomic hybridisation analysis has demonstrated copy number changes in up to 50% of cases analysed with both deletion and, more commonly, gain of material from 22q having been reported. Preliminary LOH data have proposed that allelic imbalance on 22q is more frequent in laryngeal and oral tumours than other HNSCC (dos Reis et al, 2002). Comparative genomic hybridisation analysis of 22q, along with regions of 1p, 9p, 16 and 19 can be problematic and should be interpreted with caution (Jeuken et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…In the 45 HNSCC tumours reported here, deletion of 22q was a relatively infrequent finding occurring in only eight cases; however, the clinical outcome for these patients was particularly poor. Recently, a study of 40 primary oral tumours by quantitative reverse transcriptase -polymerase chain reaction (RT -PCR) identified deletion of the DIA 1 gene, a cytochrome b5 reductase, at 22q13 in 25% of cases and this loss was also significantly associated with a decrease in survival (P ¼ 0.0018 -log rank test; Reis et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Prognostic value of genomic alterations in head and neck squamous cell carcinoma detected by comparative genomic hybridisation

et al. 2003

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A total of 45 primary head and neck squamous cell carcinomas were analysed by comparative genomic hybridisation to identify regions of chromosomal deletion and gain. Multiple regions of copy number aberration were identified including gains affecting chromosomes 3q, 8q, 5p, 7q, 12p and 11q and deletion of material from chromosomes 3p, 11q, 4p, 5q, 8p, 10q, 13q and 21. KaplanMeier survival analysis revealed significant correlations between gain of 3q25 -27 and deletion of 22q with reduced disease-specific survival. In addition, gain of 17q and 20q, deletion of 19p and 22q and amplification of 11q13 were significantly associated with reduced disease-free survival. A Cox proportional hazards regression model identified deletion of 22q as an independent prognostic marker. The data presented here provide further evidence that the creation of a genetically based tumour classification system will soon be possible, complementing current histopathological characterisation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prognostic value of genomic alterations in head and neck squamous cell carcinoma detected by comparative genomic hybridisation

et al. 2003

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“…12,14 The other MCRD/P2 region was confined to a 3 Mb physical distance at 22q13.31 that partially overlaps with an area of deletion previously detected by Oskam et al 13 The cytogenetic band at 22q13.1-3 appears to be a focal 'hot spot' for LOH in many types of human cancer, including breast, colon, ovarian, and head and neck cancers. 11,[36][37][38][39] Lida et al 10 were, in fact, able to map a 2 cM region of allelic loss in breast cancer to the same cytogenetic band. Similarly, Allione et al 11 reported six regions along chromosome 22q, ranging from 3 to 6 cM in size, two of which overlap those intervals identified in this study, and, in oral squamous cell carcinoma, allelic deletion seems to be restricted to D22S274, 39 a marker included within the region of deletion identified in our study.…”

Section: Discussionmentioning

confidence: 99%

Frequent LOH on 22q12.3 and TIMP-3 inactivation occur in the progression to secondary glioblastomas

Nakamura

Ishida

Shimada

et al. 2005

Laboratory Investigation

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Frequent allelic losses on the long arm of chromosome 22 (22q) in gliomas indicate the presence of tumor suppressor gene (TSG) at this location. However, the target gene(s) residing in this chromosome are still unknown and their putative roles in the development of astrocytic tumors, especially in secondary glioblastoma, have not yet been defined. To compile a precise physical map for the region of common deletions in astrocytic tumors, we performed a high-density loss of heterozygosity (LOH) analysis using 31 polymorphic microsatellite markers spanning 22q in a series of grade II diffuse astrocytomas, anaplastic astrocytomas, primary glioblastomas, and secondary glioblastomas that had evolved from lower grade astrocytomas. LOH was found at one or more loci in 33% (12/36) of grade II diffuse astrocytomas, in 40% (4/10) of anaplastic astrocytomas, in 41% (26/64) of primary glioblastomas, and in 82% (23/28) of secondary glioblastomas. Characterization of the 22q deletions in primary glioblastomas identified two sites of minimally deleted regions at 22q12.3-13.2 and 22q13.31. Interestingly, 22 of 23 secondary glioblastomas affected shared a deletion in the same small (957 kb) region of 22q12.3, a region in which the human tissue inhibitor of metalloproteinases-3 (TIMP-3) is located. Investigation of the promoter methylation and expression of this gene indicated that frequent hypermethylation correlated with loss of TIMP-3 expression in secondary glioblastoma. This epigenetic change was significantly correlated to poor survival in eight patients with grade II diffuse astrocytoma. Our results suggest that a 957 kb locus, located at 22q12.3, may contain the putative TSG, TIMP-3, that appears to be relevant to progression to secondary glioblastoma and subsequently to the prognosis of grade II diffuse astrocytoma. In addition, the possibility of other putative TSGs on 22q12.3-13.2 and 22q13.31 that may also be involved in the development of primary glioblastomas cannot be ruled out.

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“…Quantitative real-time RT-PCR was performed using the ABI Prism 7700 Sequence Detection System (PE Applied Biosystems), and SYBR Green I, following our previously reported protocol. 29 This fluorescent dye binds to the doublestranded DNA, allowing the quantitative detection of products during amplification by the polymerase chain reaction. Data were quantified and analyzed using Sequence Detection System software (version 1.7) from PE Applied Biosystems.…”

Section: Validation Of Microarray Datamentioning

confidence: 99%

Molecular characterization of salivary gland malignancy using the Smgb-Tag transgenic mouse model

Mäkitie

Reis

Arora

et al. 2005

Laboratory Investigation

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The molecular mechanisms underlying salivary gland tumorigenesis remain unclear. In order to identify genetic changes that occur during the development of invasive adenocarcinoma from normal salivary gland, we used the Smgb-Tag transgenic mouse model. This transgene induces the progressive development of dysplasia to invasive adenocarcinoma in the submandibular salivary gland. Gene expression patterns from 20 submandibular glands (two normal, nine dysplasia and nine adenocarcinoma samples) were assessed using a mouse 15 K cDNA array. Unsupervised hierarchical clustering was used to group gene expression based on 157 differentially expressed genes distinguishing between dysplasias and adenocarcinomas. Further analysis identified 25 significantly overexpressed and 28 underexpressed cDNA sequences in adenocarcinoma as compared to dysplasia. Differential expression of five genes (Lcn2, Ptn, Cd24a, Mapk6 and Rnps1) was validated by quantitative real-time RT-PCR in a total of 48 mouse salivary gland tissues (seven histologically normal, 13 dysplasias and 28 adenocarcinomas), including the 20 samples analyzed by cDNA arrays. Immunohistochemical analysis was used to validate the expression of Ptn and Cd24a at the protein level in a subset of 16 mouse salivary glands (four normal, five dysplasia and seven adenocarcinoma samples), as well as in 23 human submandibular gland tumors (16 pleomorphic adenomas, three adenoid cystic carcinomas, one acinic cell carcinoma, one adenocarcinoma NOS, one myoepithelial and one mucoepidermoid carcinoma). We thus demonstrated that the Smgb-Tag transgenic mouse model is a useful tool for the identification of genes that are deregulated in salivary gland adenocarcinomas. Our data suggest that Ptn and Cd24a may be genetic markers associated with salivary gland tumorigenesis and/or progression. Keywords: salivary gland; adenocarcinoma; transgenic mouse; carcinogenesis; gene expression; microarrays Salivary gland tumors are a heterogeneous and relatively rare class of head and neck cancer, with several histologically diverse subtypes, such as carcinoma ex-pleomorphic adenomas, adenoid cystic carcinomas (ACC), mucoepidermoid carcinomas (MECA) and acinic cell carcinomas (AcCA). 1 Risk factors may include external radiation to the head and neck, viral infection, and exposure to carcinogens. 2 The morphological origin and clinical behavior of these tumors differ from the majority of other head and neck tumors, which are squamous cell carcinomas; their genetic origins remain to be elucidated.

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Quantitative real-time PCR identifies a critical region of deletion on 22q13 related to prognosis in oral cancer

Cited by 44 publications

References 35 publications

Prognostic value of genomic alterations in head and neck squamous cell carcinoma detected by comparative genomic hybridisation

Prognostic value of genomic alterations in head and neck squamous cell carcinoma detected by comparative genomic hybridisation

Frequent LOH on 22q12.3 and TIMP-3 inactivation occur in the progression to secondary glioblastomas

Molecular characterization of salivary gland malignancy using the Smgb-Tag transgenic mouse model

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