Frequent allelic loss and homozygous deletion in chromosome band 8p23 in oral cancer (original) (raw)
Related papers
Oncogene, 1998
We analysed 30 primary invasive oral and laryngeal squamous carcinomas (SC), with concurrent dysplastic lesions, for genetic alterations at 15 microsatellite loci on the short arm of chromosome 8. Overall, loss of heterozygosity (LOH) was observed, in at least one informative locus, in 27% of the dysplastic lesions and in 67% of the invasive carcinomas. The highest frequency of allele losses in dysplasia (20% and 17%), and invasive carcinoma (40% and 48%) were detected in the same D8S298 and LPL-tet loci located on chromosomes 8p21 and 8p22 respectively. The minimal region with LOH was limited to 4.6 megaBases (mBs) at 8p22 and 7.1 mBs at 8p21. In addition, allelic losses in both dysplastic and corresponding invasive specimens were noted at the same loci in some tumors suggesting their emergence from a common preneoplastic clone. Allele losses correlated signi®cantly with male gender, oral and laryngeal sites and high proliferative index. The data suggest that inactivation of tumor suppressor gene(s), within these loci, may constitute an early event in the evolution of oral and laryngeal SC.
Genetic Alterations of Chromosome 8 Genes in Oral Cancer
The clinical relevance of DNA copy number alterations in chromosome 8 were investigated in oral cancers. The copy numbers of 30 selected genes in 33 OSCC patients were detected using the multiplex ligation-dependent probe amplification (MLPA) technique. Amplifications of the EIF3E gene were found in 27.3% of the patients, MYC in 18.2%, RECQL4 in 15.2% and MYBL1 in 12.1% of patients. The most frequent gene losses found were the GATA4 gene (24.2%), FGFR1 gene (24.2%), MSRA (21.2) and CSGALNACT1 (12.1%). The co-amplification of EIF3E and RECQL4 was found in 9% of patients and showed significant association with alcohol drinkers. There was a significant association between the amplification of EIF3E gene with non-betel quid chewers and the negative lymph node status. EIF3E amplifications did not show prognostic significance on survival. Our results suggest that EIF3E may have a role in the carcinogenesis of OSCC in non-betel quid chewers.
Cancer Genetics and Cytogenetics, 2007
Most human cancers are characterized by genetic instabilities. Chromosomal aberrations include segments of allelic imbalance identifiable by loss of heterozygosity (LOH) at polymorphic loci, which may be used to implicate regions harboring tumor suppressor genes. Here we performed whole genome LOH profiling on over 40 human head and neck squamous cell carcinoma (HNSCC) cell lines. Several frequent LOH regions have been identified on chromosomal arms 3p, 4p, 4q, 5q, 8p, 9p, 10p, 11q, and 17p. A genomic region of ∼7 Mb located at 8p22-p21.3 exhibits the most frequent LOH (87.9%), which suggested that this region harbors important tumor suppressor gene(s). Mitochondrial tumor suppressor gene 1 (MTUS1) is a recently identified candidate tumor suppressor gene that resides in this region. Consistent down-regulation in expression was observed in HNSCC for MTUS1 as measured by real-time quantitative RT-PCR. Sequence analysis of MTUS1 gene in HNSCC revealed several important sequence variants in the exon regions of this gene. Thus, our results suggested that MTUS1 is one of the candidate tumor suppressor gene(s) reside in 8p22-p21.3 for HNSCC. The identification of these candidate genes will facilitate the understanding of tumorigenesis of HNSCC. Further studies are needed to functionally evaluate those candidate genes.
Localization of a putative tumor suppressor gene in the sub-telomeric region of chromosome 8p
Oncogene, 1999
Several regions of chromsome arm 8p are frequently deleted in a variety of human malignancies including those of the prostate, head and neck, lung, and colon, suggesting that there is more than one tumor suppressor gene on this chromosome arm. Both laryngeal and oral squamous cell carcinomas exhibit three distinct and nonoverlapping regions of deletion on 8p. We have further re®ned the localization of the putative suppressor in 8p23 by using eight microsatellite loci to create a high resolution deletion map of 150 squamous cell carcinomas of the larynx and oral cavity. These new data demonstrate that there are two distinct classes of deletion within this relatively small region of the chromosome and suggest two possible locations for the gene within the D8S264 to D8S1788 interval. We also determined that there is little dierence between the allelic loss frequencies of microsatellites mapping near the telomeric ends of other chromosome arms and loci mapping to more centromere proximal regions of the same arm. These data suggest that the high allelic loss frequencies seen at 8p23 loci are not the result of a generalized instability of chromosome ends and are instead consistent with the activation of a speci®c suppressor gene.
2003
Detailed deletion mapping was done in the chromosomal 3p21.2-22 and 3p12-13 regions, showing high deletions in our previous study, using 13 highly polymorphic microsatellite markers in 25 primary head and neck squamous cell carcinoma (HNSCC) to narrow down the candidate tumor suppressor genes’ (TSGs) loci. Deletions in the different regions of chr.3p were seen to increase significantly with the progression of the clinical stages as detected by the fractional regional loss (FRL) index analysis. Five discrete areas with the following order of deletion frequency i.e. D3: 3p21.31 > D2: 3p21.32 > D1: 3p21.33 > D4: 3p21.2-21.1 > D5: 3p12.1, had been identified. Among these regions, the onset of deletions during progression of the tumor i.e. from stage I to stage IV, was suggested to occur in the following order i.e. D3 → D1& D2 → D4 & D5. The deletion in the D5 region was significantly associated with the progression of the clinical stages. Microsatellite size alterations (MAs...
Frequent loss of chromosome 9p21-22 early in head and neck cancer progression
Cancer research, 1994
In order to define more clearly the role of chromosome 9 loss in head and neck squamous cell carcinoma (HNSCC), 29 invasive carcinomas and 17 preinvasive lesions were analyzed for loss of heterozygosity (LOH) on chromosome 9. We found LOH in 21 of 29 (72%) HNSCC tumors using highly polymorphic microsatellite markers. In 17 of 21, LOH was found at all informative sites on the p arm with no LOH of the q arm. Further mapping in tumors, with partial LOH of the 9p arm, localized a common region of loss between markers D9S165 and D9S156. Deletion of this region on chromosome 9 has been found in several other tumor types implying the presence of a tumor suppressor gene at this locus. The inactivation of a tumor suppressor gene on chromosome 9p may represent the most commonly described genetic alteration in HNSCC. A similar incidence of allelic loss on chromosome 9p was identified in 12 of 17 (71%) preinvasive lesions. The identical frequency of loss in preinvasive and invasive lesions sugg...
Loss of heterozygosity of the short arm of chromosomes 3 and 9 in oral cancer
International Journal of Cancer, 1996
Loss of heterozygosity (LOH) on chromosomes 3p and 9p has been documented in a variety of malignancies, which suggests the presence of tumor suppressor gene loci on these chromosomes. We have studied 77 oral carcinomas for LOH using 16 microsatellite markers distributed over 5 human chromosomes.
Oral Oncology, 2007
We analysed the loss of heterozygosity (LOH) of long arm of chromosome 2 by using 16 polymorphic microsatellite markers in 39 matched oral normal and cancer tissues, and defined the deletional mapping of the region with putative tumor suppressor genes. LOH was detected at least one location in 33 of 39 (85%) tumor tissues. Frequent deletions were detected at the locations of microsatellite markers, D2S2304 (35%), D2S111 (40%), D2S155 (35%), D2S1327 (29%), D2S164 (29%), D2S125 (68%) and D2S140 (32%). Three preferentially deleted regions at 2q21-24, 2q33-35 and 2q37.3 were observed. Several candidate tumor suppressor genes in these regions such as LRP1B, CASP8, CASP10, BARD1, ILKAP, PPP1R7, and ING5, are located. Further molecular analysis of each gene should be performed to clarify their roles in oral carcinogenesis.
A Short Review of the Role of Genetic in Oral and Squamous Cell Carcinoma
2020
This review aimed to analyze the role of genetic in oral cancer. Head and Neck cancer is multifactorial disease in which a wide factors play a role in its apparition and progress. More than 90% of malignant neoplasms are oral squamous cell carcinoma developed on the mucous epithelium and the sixth most common cancer in the world. The environment, such as smokeless tobacco, alcohol, betel quid chewing are most common factors are involved in the etiology of the oral cancer. Several genes and pathways associated with oral squamous cell carcinoma are significant in terms of early detection and prognosis. Molecular biomarkers are being discovered in oral cancer diagnostic. It could be used as screening for detection and improve therapeutic strategies of oral pre-cancer and oral squamous cell carcinoma.
Head and neck squamous cell carcinoma (HNSCC) is a frequent malignancy with a poor survival rate. Identifying the tumor suppressor gene (TSG) loci by genomic studies is an important step to uncover the molecular mechanisms involved in HNSCC pathogenesis. Therefore, comprehensive analyses were performed to 170 subjects. They were 41 premalignat patients, 79 malignant patients, and 50 control subjects. The chromosomal aberrations included Translocation which ranged from 4.8% and 19% in premalignant and malignant HNSCCs, respectively. Gain ranged from 19.5% to 52%. While loss was found to be higher 29.3 and 87 in both. Duplication and breakpoint ranged 19.5% to 59.5% and 24.3% to 35.4% for premalignant and HNSCC, respectively. Loss of heterozygosity (LOH) and microsatellite instability (MSI) were detected and showed an allelic imbalance mainly in six regions (3pter-3p24.2, 5q33.3-q34, 9p21, 9q21.1-22.3, 17p, and 17p12) of chromosomes 3, 5, 9 and 17 in premalignant, and HNSCC patients c...