The human telomerase gene: complete genomic sequence and analysis of tandem repeat polymorphisms in intronic regions

Leem, Sun‐Hee; Londoño-Vallejo, J. Arturo; Kim, Jung-Hyun; Bui, Hung; Tubacher, Emmanuel; Solomon, Greg; Park, Jung‐Eun; Horikawa, Izumi; Kouprina, Natalay; Barrett, J. Carl; Larionov, Vladimir

doi:10.1038/sj.onc.1205122

Cited by 72 publications

(71 citation statements)

References 44 publications

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“…Recently, we demonstrated a relationship between cancer predisposition and minisatellite (VNTR, variable number of tandem repeats) variants. Rare alleles of minisatellites are associated with a high risk for various types of cancer (20)(21)(22)(23)(24). These data lend support to the concept that biologically significant consequences might result from variations in a minisatellite locus and suggests a biological basis for some cancer predisposition.…”

Section: Introductionsupporting

confidence: 63%

Susceptibility for breast cancer in young patients with short rare minisatellite alleles of BORIS

Yoon¹,

Kim²,

Cho³

et al. 2010

BMB Reports

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In this study, we characterized two blocks of minisatellites in the 5' upstream region of the BORIS gene (BORIS-MS1, -MS2). BORIS-MS2 was found to be polymorphic; therefore, this locus could be useful as a marker for DNA fingerprinting. We assessed the association between BORIS-MS2 and breast cancer by a case-control study with 428 controls and 793 breast cancers cases. Rare alleles in the younger group (age, ＜40) were associated with a statistically significant increased risk of breast cancer (odds ratio, 4.84; 95% confidence interval, 1.06-22.22; and P = 0.026). A statistically significant association between the short rare alleles and cancer was identified in the younger group (8.02; 1.01-63.83; P = 0.021). Kaplan-Meier estimates showed that poor prognosis was associated with patients who contained the rare alleles. Our data suggest that the short rare alleles of BORIS-MS2 could be used to identify the risk for breast cancer in young patients. [BMB reports 2010; 43(10): 698-703]

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Section: Introductionsupporting

confidence: 63%

Susceptibility for breast cancer in young patients with short rare minisatellite alleles of BORIS

Yoon¹,

Kim²,

Cho³

et al. 2010

BMB Reports

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“…This tumor contained an integration of HPV18 into the hTERT gene (Figure 3a). The proximal viral-host junction identified in MC11 was at nucleotide 16102 of GenBank sequence AY007685, approximately 8.3 kb proximal to the hTERT transcription start site (located at nucleotide 24442 of AY007685) (Leem et al, 2002). We rescued the distal end of this integration using longrange PCR and sequenced the integrated HPV18 sequence.…”

Section: Resultsmentioning

confidence: 99%

Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers

et al. 2003

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Chronic infections with the hepatitis B virus (HBV) and high-risk human papillomaviruses (HPVs) are important risk factors for hepatocellular carcinoma (HCC) and cervical cancer (CC), respectively. HBV and HPV are DNA viruses that almost invariably integrate into the host genome in invasive tumors. The viral integration sites occur throughout the genome, leading to the presumption that there are no preferred sites of integration. A number of viral integrations have been shown to occur within the vicinity of important cancer-related genes. In studies of HBV-induced HCC and HPV-induced CC, we have identified two HBV and three HPV integrations into the human telomerase reverse transcriptase (hTERT) gene. Detailed characterization of the integrations revealed that four integrations occurred within the hTERT promoter and upstream region and the fifth integration occurred in intron 3 of the hTERT gene. None of the integrations altered the hTERT coding sequence and all resulted in juxtaposition of viral enhancers near hTERT, with potential activation of hTERT expression. Our work supports the hypothesis that the sites of oncogenic viral integration are nonrandom and that genes at the sites of viral integration may play important roles in carcinogenesis.

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“…However, there were only minor variations and one deletion seen in the 38 colon carcinomas analysed, which led the authors to conclude that the size rearrangements of the hTERT minisatellites are not required for telomerase expression in colon carcinomas (Szutorisz et al, 2001). However, in a recent work, eight alleles of intron 6 VNTR and four alleles of intron 2 VNTR in hTERT gene locus were identified among 103 unrelated individuals, and in one patient with a kidney tumor, the VNTR in intron 6 was found to have undergone concomitant rearrangements, suggesting that chromosomal rearrangements of these VNTR may be associated with the activation of hTERT in cancer cells (Leem et al, 2002). Consistent with the above reports, we also found rearrangement of the MNS16A VNTR in 11 primary lung tumors examined in our another study (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Association of a functional tandem repeats in the downstream of human telomerase gene and lung cancer

et al. 2003

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Chemoprevention has been widely explored as a promising strategy for controlling the incidence of lung cancer, the leading cause of cancer-related death. To maximize the benefit of lung cancer chemoprevention, it is important to identify individuals at high risk for the disease. The genetic background has been shown to play an important role in one's risk of developing lung cancer. We report here the identification of a polymorphic tandem repeats minisatellite (termed MNS16A) in the downstream region of the human telomerase gene. This minisatellite is located upstream of an antisense transcript from the human telomerase gene locus and was demonstrated to have promoter activity. The promoter activity was significantly lower in the construct containing the shorter repeats, suggesting that the MNS16A variant may have a relevance of functionality. To explore the role of this novel polymorphism in lung cancer, we conducted a pilot hospital-based case-control study by identifying the MNS16A genotype with genomic DNA from 53 lung cancer patients and 72 cancer-free controls. We found four different alleles and classified them as shorter (S) or longer (L) on the functional basis of the length of the repeats in the controls. The MNS16A genotype distributions of the SS, SL, and LL genotypes were 11, 32, and 57%, respectively, in the cases, and 14, 40, and 46%, respectively, in the controls. Compared with the SS þ SL genotype, the LL genotype was associated with greater than twofold increased risk of lung cancer (odds ratio ¼ 2.18; 95% confidence interval ¼ 0.92, 5.20) after adjustment for age, sex, ethnicity, and smoking status, suggesting a potential role of MNS16A in lung cancer susceptibility. Larger studies are needed to verify our findings.

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The human telomerase gene: complete genomic sequence and analysis of tandem repeat polymorphisms in intronic regions

Cited by 72 publications

References 44 publications

Susceptibility for breast cancer in young patients with short rare minisatellite alleles of BORIS

Susceptibility for breast cancer in young patients with short rare minisatellite alleles of BORIS

Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers

Association of a functional tandem repeats in the downstream of human telomerase gene and lung cancer

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