Frequent inactivation of RASSF1A, BLU, and SEMA3B on 3p21.3 by promoter hypermethylation and allele loss in non-small cell lung cancer

Ito, Masao; Ito, Genshi; Kondo, Masashi; Uchiyama, Mineto; Fukui, Takayuki; Mori, Satoshi; Yoshioka, Hide; Ueda, Yuichi; Shimokata, Kaoru; Sekido, Yoshitaka

doi:10.1016/j.canlet.2004.10.041

Cited by 74 publications

(71 citation statements)

References 30 publications

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“…However, in NSCLC an association was found (Agathanggelou et al, 2003b). This data is further supported in a report by Ito et al (2005), which shows that in NSCLC coincident methylation of two of the three genes SEMA3B (located within the larger B250 kb deletion region at 3p21.3), BLU/ZMYND10 or RASS-F1A was significantly associated. In a recent study of neuroblastoma tumours, methylation of both RASSF1A and BLU/ZMYND10 appear associated (Abe et al, 2005).…”

Section: Apoptosis Microtubule Dynamics Cell Cycle Arrestsupporting

confidence: 81%

“…Promoter CpG island hypermethylation is coincident with loss of BLU/ZMYND10 expression, which can be restored following treatment with the DNA demethylating agent 5-aza-2 0 -deoxycytidine (5azaDC) (Agathanggelou et al, 2003b;Hesson et al, 2004;Qiu et al, 2004;Yau et al, 2006;Yi Lo et al, 2006). BLU/ZMYND10 hypermethylation and downregulation has been described as a frequent event in primary tumours such as glioma (80%), cervical squamous cell carcinomas (77%), NPC (66%), neuroblastoma (41-70%) and NSCLC (19-43%) with lower frequencies observed in gall bladder carcinomas (26%), ependymomas (13.6%) and SCLC (14%) (Agathanggelou et al, 2003b;Hesson et al, 2004;Qiu et al, 2004;Abe et al, 2005;Ito et al, 2005;Marsit et al, 2005;Lai et al, 2006;Michalowski et al, 2006;Riquelme et al, 2007). In some tumour types, BLU/ZMYND10 methylation is an early event detectable in stage II glioma and stage I/II cervical squamous cell carcinomas (at frequencies of 88 and 85/68%, respectively) Lai et al, 2006).…”

Section: Rassf1mentioning

confidence: 99%

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Evaluation of the 3p21.3 tumour-suppressor gene cluster

2007

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Section: Apoptosis Microtubule Dynamics Cell Cycle Arrestsupporting

confidence: 81%

Section: Rassf1mentioning

confidence: 99%

Evaluation of the 3p21.3 tumour-suppressor gene cluster

2007

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“…To date, the prevalence of RASSF1A methylation is exhibited in 30-40% of NSCLC, and is mainly detected by methylation-specific PCR (MSP) analysis Toyooka et al, 2003;Guo et al, 2004;Wang et al, 2004;Choi et al, 2005;Dammann et al, 2005;Ito et al, 2005;Chen et al, 2006;Hsu et al, 2007;Yanagawa et al, 2007;Yang et al, 2007;Liu et al, 2008;Lin et al, 2009;Peng et al, 2010;Zhang et al, 2010;Kang et al, 2011;Song et al, 2011;. However, association of RASSF1A promoter methylation with NSCLC have mostly been investigated in studies with small sample sizes or other limitations in study design, leading to conflicting results, especially in the relationship between RASSF1A promoter methylation and clinicopathologic features among NSCLC.…”

Section: Associations Between Rassf1a Promoter Methylation and Nsclc:mentioning

confidence: 99%

“…Moreover, one was excluded as a duplicate publication . Ultimately, 19 publications met the inclusion criteria (Figure 1) Toyooka et al, 2003;Guo et al, 2004;Wang et al, 2004;Choi et al, 2005;Dammann et al, 2005;Ito et al, 2005;Chen et al, 2006;Hsu et al, 2007;Kim et al, 2007;Yanagawa et al, 2007;Yang et al, 2007;Liu et al, 2008;Lin et al, 2009;Peng et al, 2010;Zhang et al, 2010;Kang et al, 2011;Song et al, 2011;Li et al, 2012) and were included in the meta-analysis. Detailed characteristics of the 19 studies are listed in Table 1.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Detailed characteristics of the 19 studies are listed in Table 1. Overall, 5 of the included articles were published in Chinese Peng et al, 2010;Zhang et al, 2010;Kang et al, 2011;Song et al, 2011), and the others were published in English Toyooka et al, 2003;Guo et al, 2004;Wang et al, 2004;Choi et al, 2005;Dammann et al, 2005;Ito et al, 2005;Chen et al, 2006;Hsu et al, 2007;Yanagawa et al, 2007;Liu et al, 2008;Li et al, 2012). The aforementioned 19 studies provided data regarding RASSF1A promoter methylation in 2063 cases of NSCLC tissues and 1184 controls of non-tumor tissues, with a total sample size of 3247 cases.…”

Section: Study Characteristicsmentioning

confidence: 99%

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Associations Between RASSF1A Promoter Methylation and NSCLC: A Meta-analysis of Published Data

Liu¹,

Tan²,

Guo³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: RASSF1A has been reported to be a candidate tumor suppressor in non-small cell lung cancer (NSCLC). However, the association between RASSF1A promoter methylation and NSCLC remains unclear, particularly in regarding links to clinicopathologic features. Methods: Eligible studies were identified through searching PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases. Studies were pooled and odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also performed to evaluate publication bias. Keywords: RAS associations domain family protein 1A -non-small cell lung cancer -methylation -odds ratio

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Epigenetic modulation of endogenous tumor suppressor expression in lung cancer xenografts suppresses tumorigenicity

Cantor

Iliopoulos

Rao

et al. 2006

Intl Journal of Cancer

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Epigenetic changes involved in cancer development, unlike genetic changes, are reversible. DNA methyltransferase and histone deacetylase inhibitors show antiproliferative effects in vitro, through tumor suppressor reactivation and induction of apoptosis. Such inhibitors have shown activity in the treatment of hematologic disorders but there is little data concerning their effectiveness in treatment of solid tumors. FHIT, WWOX and other tumor suppressor genes are frequently epigenetically inactivated in lung cancers. Lung cancer cell clones carrying conditional FHIT or WWOX transgenes showed significant suppression of xenograft tumor growth after induction of expression of the FHIT or WWOX transgene, suggesting that treatments to restore endogenous Fhit and Wwox expression in lung cancers would result in decreased tumorigenicity. H1299 lung cancer cells, lacking Fhit, Wwox, p16 INK4a and Rassf1a expression due to epigenetic modifications, were used to assess efficacy of epigenetically targeted protocols in suppressing growth of lung tumors, by injection of 5-aza-2-deoxycytidine (AZA) and trichostatin A (TSA) in nude mice with established H1299 tumors. High doses of intraperitoneal AZA/TSA suppressed growth of small tumors but did not affect large tumors (200 mm 3 ); lower AZA doses, administered intraperitoneally or intratumorally, suppressed growth of small tumors without apparent toxicity. Responding tumors showed restoration of Fhit, Wwox, p16 INKa , Rassf1a expression, low mitotic activity, high apoptotic fraction and activation of caspase 3. These preclinical studies show the therapeutic potential of restoration of tumor suppressor expression through epigenetic modulation and the promise of re-expressed tumor suppressors as markers and effectors of the responses. ' 2006 Wiley-Liss, Inc.Key words: DNA methylation; tumor suppressor genes; 5-aza-2-deoxycytidine Lung cancer is the leading cause of cancer death in the western hemisphere for men and women, eclipsing the combined mortalities from breast, colon and prostate cancers. Genomic aberrations involving chromosome 3p are the most frequent and earliest genetic events in lung carcinogenesis. 1,2 In particular, the FHIT gene, spanning the human common fragile site, FRA3B, at chromosome 3p14.2, and the RASSF1A gene at 3p21 are frequently silenced in lung cancer and show hallmarks of tumor suppressor genes. 3 FHIT is altered in many other types of cancers, including breast, head and neck, cervical, bladder, esophageal, gastric, pancreatic and renal cancer and alterations occur in very early stages of preneoplasia in some organs. Fhit loss is associated with progression and outcome in cancers of various organs. 4 Similarly, the WWOX gene at FRA16D is frequently silenced in lung cancers, and has recently been shown to suppress growth of lung cancer cells in nude mice. [5][6][7] The RASSF1A promoter region is hypermethylated in a large fraction of lung and other cancers 8,9 and methylation of the RASSF1A regulatory region has been proposed as a biomarker of lung ca...

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Frequent inactivation of RASSF1A, BLU, and SEMA3B on 3p21.3 by promoter hypermethylation and allele loss in non-small cell lung cancer

Cited by 74 publications

References 30 publications

Evaluation of the 3p21.3 tumour-suppressor gene cluster

Evaluation of the 3p21.3 tumour-suppressor gene cluster

Associations Between RASSF1A Promoter Methylation and NSCLC: A Meta-analysis of Published Data

Epigenetic modulation of endogenous tumor suppressor expression in lung cancer xenografts suppresses tumorigenicity

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