Location of candidate tumour suppressor gene loci at chromosomes 3p, 8p and 9p for oral squamous cell carcinomas

Partridge, M; Emilion, G; Pateromichelakis, S.; Phillips, Elaine; Langdon, John H.

doi:10.1002/(sici)1097-0215(19991029)83:3<318::aid-ijc6>3.0.co;2-v

Cited by 54 publications

(31 citation statements)

References 18 publications

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“…However, few genes implicated in oral tumorigenesis have been identified in these studies. For example, allelic imbalances of p16 (CDKN2A) and FHIT loci have been associated with these chromosomal alterations and have been implicated in OSCC development (13,14).…”

Section: Introductionmentioning

confidence: 99%

Loss of 3p26.3 is an independent prognostic factor in patients with oral squamous cell carcinoma

et al. 2011

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Abstract. Oral squamous cell carcinoma (OSCC) is a common malignancy worldwide and the prognosis for patients with advanced-stage OSCC is particularly poor. To identify DNA copy number aberrations and candidate genes associated with a poor or favorable outcome, we analyzed the genome profiles of OSCC tumors by array-based comparative genomic hybridization (A-CGH). This technique uses DNA microarray technology to detect genomic copy number variations at a higher resolution level than chromosome-based CGH. Fifty patients with primary OSCCs were included in the study. Of these 50 patients, 37 were treated surgically and 13 were treated without surgery and had received irradiation and/or chemotherapy. All samples were analyzed by A-CGH. Gains were detected frequently (>50%) at chromosomal regions 5p15. 33, 7p22.3, 8q21.1-24.3, 9q34.3, 11q13, 16p13.3 and 20q13.3. Losses were frequently detected at 3p22, 3p14 and 4q35.2. High-level gains were recurrently (>10%) detected at each of 5p15, 7p22, 7p11, 8q24, 11q13, 11q22 and 22q11. Gains of 2p25.1, 11p15, 16p13.3, 16q24.3 and 20q13.3 were inversely correlated with nodal metastasis. In 37 of the 50 OSCC patients treated with surgery, gains of 8q12.1-24.22 and losses of 3p26.2-3 were associated with disease-specific survival (p<0.01). Loss of a 0.2 Mb chromosomal region in 3p26.3 was associated with a poor prognostic outcome in the Kaplan-Meier analysis (p<0.01 by the log-rank test). Multivariate analysis revealed that loss of 3p26.3 is an independent prognostic factor (p<0.01) of OSCC. Loss of a 0.2 Mb chromosomal region in 3p26.3 including the CHL1 (cell adhesion molecule with homology to L1CAM1) gene was identified as a novel potential marker for predicting the prognosis of patients with OSCC.

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Section: Introductionmentioning

confidence: 99%

Loss of 3p26.3 is an independent prognostic factor in patients with oral squamous cell carcinoma

et al. 2011

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“…Loss of heterozygosity (LOH) at multiple chromosome regions and genetic and epigenetic alterations of several proto-oncogenes and tumour suppressor genes have been demonstrated in oral carcinomas, including alterations of the TP53, p16, p15, MGMT, Ecadherin genes and RAS (Califano et al, 1996;Partridge et al, 1999;Williams, 2000;Ogi et al, 2002;Viswanathan et al, 2003). In addition, our previous study showed that hypermethylation of the ABO gene promoter was associated with loss of expression of A/B antigen in approximately one-third of oral squamous cell carcinomas (Gao et al, 2004).…”

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confidence: 96%

Loss of heterozygosity at 9q33 and hypermethylation of the DBCCR1 gene in oral squamous cell carcinoma

Worm

Guldberg

et al. 2004

Br J Cancer

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The DBCCR1 gene at chromosome 9q33 has been identified as a candidate tumour suppressor, which is frequently targeted by promoter hypermethylation in bladder cancer. Here, we studied the possible involvement of DBCCR1 in the development of oral squamous cell carcinoma. DNA from 34 tumours was examined for loss of heterozygosity (LOH) at three markers surrounding DBCCR1 and for hypermethylation of the DBCCR1 promoter, using methylation-specific PCR and methylation-specific melting-curve analysis. LOH was found in 10 of 31 cases (32%), and DBCCR1 hypermethylation was present in 15 of 34 cases (44%). Hypermethylation of DBCCR1 was also present in three of seven epithelial tissues adjacent to the tumours, including two hyperplastic and one histologically normal epithelia. Furthermore, of four oral leukoplakias with dysplasia, one showed LOH at 9q33 and two showed DBCCR1 hypermethylation. These data suggest that LOH at 9q33 and hypermethylation of the DBCCR1 promoter are frequent and possibly early events in oral malignant development. Oral cancer comprises about 3% of all newly diagnosed cancer cases in the Western countries. Despite advances in therapy, the 5-year survival rate after diagnosis is still poor and remains B50% (Landis et al, 1999;Silverman, 2001). Clinically, oral carcinomas often develop in a two-step process. The first step is characterised by the appearance of potentially malignant lesions such as leukoplakias and erythroplakias, and the second step is characterised by the development of carcinomas. However, clinical and histopathological features are insufficient measures for predicting the prognosis of potentially malignant lesions (Warnakulasuriya, 2000(Warnakulasuriya, , 2001. Furthermore, a recent study indicated that clinically and histologically normal mucosa adjacent to tumours may harbour patches of genetically altered cells (Braakhuis et al, 2003). It is, therefore, important to find molecular markers for identifying the minor fraction of oral lesions that will develop into carcinoma.Loss of heterozygosity (LOH) at multiple chromosome regions and genetic and epigenetic alterations of several proto-oncogenes and tumour suppressor genes have been demonstrated in oral carcinomas, including alterations of the TP53, p16, p15, MGMT, Ecadherin genes and RAS (Califano et al, 1996;Partridge et al, 1999;Williams, 2000;Ogi et al, 2002;Viswanathan et al, 2003). In addition, our previous study showed that hypermethylation of the ABO gene promoter was associated with loss of expression of A/B antigen in approximately one-third of oral squamous cell carcinomas (Gao et al, 2004). LOH at 9q34, in which the ABO gene is located, was also a frequent event in these tumours. However, a number of tumours from AO and BO heterozygotes showed deletion of the O allele, which does not encode a functional glycosyltransferase, suggesting the existence of an additional tumour suppressor gene on chromosome 9q. The DBCCR1 (deleted in bladder cancer chromosomal region candidate 1) gene at chromosome 9q33 was identified as...

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“…[5][6][7][8][9] Tumor-suppressor gene inactivation has been associated with oral dysplasia and squamous cell carcinoma, most commonly involving loci on chromosomes 3p, 9p, and 17p, although many others have been described. 2,[10][11][12][13][14][15][16][17][18][19][20][21][22][23] The function of the tumor-suppressor genes located on chromosome 3p are currently poorly defined, whereas the functions of p16 (also known as CDKN2A, located on 9p21) and p53 (located on 17p13) are well established. Inactivation of these genes causes altered expression of their respective gene products p16…”

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confidence: 99%

Immunohistochemical detection of p16INK4a in dysplastic lesions of the oral cavity

2006

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Significant intra-and interobserver variability exists in diagnosing and grading oral epithelial dysplasia. Mutations in the tumor-suppressor gene p16 are common in oral cavity dysplastic lesions, but whether immunohistochemical detection of the gene product p16INK4a (p16) can be used as a reliable biomarker for dysplasia is unclear. In total, 119 biopsy specimens representing various oral cavity sites and degrees of dysplasia were retrieved from the pathology files of Emory University Hospital. Formalin-fixed, paraffinembedded sections were stained with hematoxylin and eosin (H&E) and with a monoclonal antibody to p16 (LabVision Corporation, Clone JC2). A blinded review of the H&E slides and the pattern and degree of p16 expression was independently performed by two pathologists. A consensus was obtained when diagnoses differed. Morphologic diagnoses were then compared to p16 immunohistochemical expression. Overall, 61/119 (51%) cases showed no p16 immunoreactivity, including 12/33 (36%) cases of no dysplasia, 11/28 (39%) cases of mild dysplasia, and 38/58 (66%) cases of moderate/severe dysplasia. The remaining cases showed p16 expression limited to the basal and suprabasal nuclei and generally confined to the lower one-third of the epithelium. A logistic regression model showed a trend toward absent p16 expression with increasing severity of dysplasia (P ¼ 0.006). Decreased expression of p16 in dysplastic lesions, as found in this study, may reflect the biologic events involving loss of p16 gene function in the pathogenesis of oral cancer. Our findings suggest that p16 immunohistochemistry is not helpful in differentiating dysplastic from nondysplastic mucosa in oral cavity biopsies, and thus is not a reliable biomarker for use in routine clinical practice.

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Location of candidate tumour suppressor gene loci at chromosomes 3p, 8p and 9p for oral squamous cell carcinomas

Cited by 54 publications

References 18 publications

Loss of 3p26.3 is an independent prognostic factor in patients with oral squamous cell carcinoma

Loss of 3p26.3 is an independent prognostic factor in patients with oral squamous cell carcinoma

Loss of heterozygosity at 9q33 and hypermethylation of the DBCCR1 gene in oral squamous cell carcinoma

Immunohistochemical detection of p16INK4a in dysplastic lesions of the oral cavity

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