Structure and Methylation-Associated Silencing of a Gene within a Homozygously Deleted Region of Human Chromosome Band 8p22

MacGrogan, Donal; Levy, Alina; Bova, G. Steven; Isaacs, William B.; Bookstein, Robert

doi:10.1006/geno.1996.0322

Cited by 111 publications

(76 citation statements)

References 5 publications

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“…The etiological and clinical signi®cance of these results are unclear and deserve further studies. Our results also show signi®cant correlation between 8p alterations and high proliferative index which corroborates previous investigations of these regions in other tumors and indicates a possible association between abnormal cell cycle regulation and aggressive clinical behavior (Li et al, 1994;MacGrogan et al, 1996;Merlo et al, 1992).…”

Section: Discussionsupporting

confidence: 92%

Localization of chromosome 8p regions involved in early tumorigenesis of oral and laryngeal squamous carcinoma

et al. 1998

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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.

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Section: Discussionsupporting

confidence: 92%

Localization of chromosome 8p regions involved in early tumorigenesis of oral and laryngeal squamous carcinoma

et al. 1998

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“…N33, which shares homology with the oligosaccharyl transferase enzyme, is frequently methylated in colorectal tumors (MacGrogan et al, 1996) and becomes methylated in normal colonic tissues as a function of age (Issa, JPJ, unpublished observations). While the functional signi®cance of N33 methylation in GBM remains unclear, its association with age and its striking concordance with ER methylation provide interesting clues as to the mechanism of cancer-related methylation.…”

Section: Discussionmentioning

confidence: 99%

“…The six genes chosen for this study were: The estrogen receptor gene (ER), which is methylated in normal colon as a function of age (Issa et al, 1994) and which is hypermethylated in a large number of neoplasms; HIC1 (Hypermethylated in Cancer 1), a candidate tumor-suppressor gene cloned because of the presence of a CpG island on 17p13.3 which is hypermethylated in many neoplasms (Wales et al, 1995); The N33 gene, which was recently identi®ed from an area of frequent allelic losses in prostate cancer and which is hypermethylated in colon cancer (MacGrogan et al, 1996). The P15 and P16 genes which function as inhibitors of cell cycle progression and have tumor-suppressor properties (Kamb, 1995); and as a control, the c-abl gene.…”

Section: Methylation Status Of Multiple Cpg Islands In Normal Brainmentioning

confidence: 99%

Concordant methylation of the ER and N33 genes in glioblastoma multiforme

Jedlicka

Ahuja

et al. 1998

Oncogene

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Methylation of promoter-associated CpG islands appears to be a potential way by which tumor suppressor genes are inactivated in cancer. Using Southern blot analysis, we have studied the methylation of several genes in glioblastoma multiforme (GBM), trying to determine their contribution to tumorigenesis. Genes studied included the estrogen receptor (ER), N33, the candidate tumor-suppressors P15, P16 and HIC1 and a control gene, c-abl. Hypermethylation of N33, ER, HIC1, P16, P15 and c-abl were found in 61%, 59%, 60%, 5%, 2% and 0% of GBM respectively. HIC1 methylation was detected in normal brain as well, but appeared to be more extensive in tumors. ER and N33 methylation were signi®cantly more frequent in tumors from individuals over the age of 40 (70% and 88% vs 36% and 14%). In addition, there was a strong association between ER and N33 methylation, which were concordant in 81% of the cases (P50.01). ER and N33 methylation in GBM may therefore appear as a result of shared etiologic factors, which may relate in part to aging cell populations in the brain.

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“…Chromosomal region 8p22 contains the known putative TSGs MSR1 and N33. 22,23 He et al 24 mapped the NKX3.1 gene to 8p21, which is a human prostate-specific, androgen-regulated homeobox gene. Many studies indicate that loss of 8p12-21 is an early event in prostate carcinogenesis, whereas loss of 8p22 is a later event that is common in advanced prostate cancers.…”

Section: Chromosomal Lossesmentioning

confidence: 99%

Genetic changes in pT2 and pT3 prostate cancer detected by comparative genomic hybridization

Fukasawa

Kino

Kobayashi

et al. 2007

Prostate Cancer Prostatic Dis

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Prostate-specific antigen (PSA) screening has led to a remarkable increase in prostate cancer cases undergoing operative therapy. Over half of patients with locally advanced cancer (^pT3) develop rising PSA levels (biochemical failure) within 10 years. It is very difficult to predict which patients will progress rapidly to advanced disease following biochemical failure (BF). Therefore, a more useful prognostic factor is needed to suggest the most appropriate therapies for each patient. To determine chromosomal aberrations, we examined 30 patients with stage pT2 or pT3 primary prostate adenocarcinomas and no metastases (pN0M0) by comparative genomic hybridization (CGH). Laser capture microdissection (LCM) was used to gather cancer cells from frozen prostate specimens. Common chromosomal alterations included losses on 2q23-24, 4q26-28, 6q14-22, 8p12-22 and 13q21-31, as well as gains on 1p32-36, 6p21 and 17q21-22. Losses at 8p12-22 and 13q21-31 were observed more frequently in pT3 than pT2 tumors (Po0.05 and Po0.01, respectively). Losses at 8p12-22 were more frequent in tumors with BF (Po0.05), and those at 13q12-21 were more frequent in tumors with Gleason score (GS) 7 or more than lower GS (Po0.05). These findings suggest that losses of 8p12-22 and 13q21-31 are important determinants of prostate cancer progression.

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Structure and Methylation-Associated Silencing of a Gene within a Homozygously Deleted Region of Human Chromosome Band 8p22

Cited by 111 publications

References 5 publications

Localization of chromosome 8p regions involved in early tumorigenesis of oral and laryngeal squamous carcinoma

Localization of chromosome 8p regions involved in early tumorigenesis of oral and laryngeal squamous carcinoma

Concordant methylation of the ER and N33 genes in glioblastoma multiforme

Genetic changes in pT2 and pT3 prostate cancer detected by comparative genomic hybridization

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