Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns.

Sekido, Yoshitaka; Bader, Scott; Latif, Farida; Chen, Jeou Yuan; Duh, Fuh Mei; Wei, Ming Hui; Albanesi, Joseph P.; Lee, Cheng‐Chi; Lerman, Michael I.; Minna, John D.

doi:10.1073/pnas.93.9.4120

Cited by 216 publications

(142 citation statements)

References 26 publications

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“…Previous studies have demonstrated that mutations in the SEMA3B gene are infrequent events. Sekido et al 2 and Kuroki et al 15 reported that loss of SEMA3B mRNA expression was detected in approximately 50% of non small cell lung cancer, which was caused by SEMA3B promoter hypermethylation. Conversely, the tumor suppressor effect could be restored by adenovirus-mediated expression of genes located on chromosome 3p.21.3.…”

Section: Discussionmentioning

confidence: 99%

“…MSP was performed using specific primers and conditions already described. 2,3,8,15,19,24 Detailed primer sequences are available on request. Briefly, a 20 ml reaction volume contained 150 ng bisulfite-modified DNA, 1 Â PCR buffer, 1.5 mM MgCl 2 , 0.16 mM dNTPs, 0.25 mM specific primer mix (forward and reverse primers) and 1 unit Taq enzyme (Roche, Mannheim, Germany).…”

Section: Methylation Analysismentioning

confidence: 99%

“…A group of candidate tumor suppressor genes (designated BLU, SEMAPHORIN 3B, or RASSF1A) has recently been mapped to this critical gene-rich region. 2,[11][12][13] SEMAPHORIN 3B (SEMA3B) is a member of the semaphorin family, which is also located on 3p21.3. Semaphorins are a family of signaling molecules initially identified to play a role in axonal guidance and can be classified as either membrane-bound (classes 1, 4, 5 and 6) or secreted (classes 2 and 3).…”

mentioning

confidence: 99%

“…The short arm of chromosome 3 has been shown to exhibit loss of heterozygosity (LOH) in several types of cancer, including ovarian, kidney, lung, nasopharyngeal and also liver cancer. 1,2 In particular, overlapping homozygous deletions in lung cancers have been identified in region 3p21.3. 3,4 In HCC, LOH of chromosome 3p occurred in about 30% of the patients.…”

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confidence: 99%

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Allele loss and epigenetic inactivation of 3p21.3 in malignant liver tumors

Tischoff

Markwarth

Witzigmann

et al. 2005

Intl Journal of Cancer

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Previously, the RASSF1A, BLU and SEMAPHORIN 3B (SEMA3B) candidate tumor suppressor genes on chromosome 3p21.3 were found to be inactivated and downregulated by genetic and epigenetic changes in lung cancer. We analyzed the methylation status of RASSF1A, BLU and SEMA3B in 35 hepatocellular carcinomas (HCCs) and 15 cholangiocarcinomas (CCs) by methylationspecific PCR and loss of heterozygosity (LOH) at 3p21.3 after microdissection. The presence of mRNA transcripts was confirmed by semiquantitative PCR. SEMA3B hypermethylation was found in 29/35 HCCs (83%) and in all (15/15) patients with CC. BLU promoter hypermethylation was detected in 7/35 (20%) HCCs and 3/15 (20%) CCs. In 2 corresponding specimens of hepatitis B virus-related liver cirrhosis, BLU methylation was also observed, but not in uninvolved normal liver tissue. RASSF1A was methylated in 21/35 HCCs (60%) and in 10/15 CCs (67%). LOH at 3p21.3 occurred in 8/35 (23%) HCCs and 3/15 (20%) CCs. The presence of hypermethylation was statistically associated with LOH of SEMA3B and correlated with downregulation of mRNA transcripts. SEMA3B transcripts increased upon treatment of HCC cell lines with the demethylation compound 5-aza-2-deoxycytidine. In conclusion, our data indicate that 2-hit gene silencing of SEMA3B through epigenetic changes and allele loss is a common and important event in the carcinogenesis of malignant liver tumors. ' 2005 Wiley-Liss, Inc.Key words: hepatocellular carcinoma; cholangiocarcinoma; methylation; loss of heterozygosity; BLU; SEMA3B; RASSF1A Primary liver cancer is one of the most frequent carcinomas worldwide. Besides hepatocellular carcinoma (HCC), accounting for 80-90% of all primary liver cancers, cholangiocarcinoma (CC) is the second most common primary hepatic malignancy. The short arm of chromosome 3 has been shown to exhibit loss of heterozygosity (LOH) in several types of cancer, including ovarian, kidney, lung, nasopharyngeal and also liver cancer. 1,2 In particular, overlapping homozygous deletions in lung cancers have been identified in region 3p21.3. 3,4 In HCC, LOH of chromosome 3p occurred in about 30% of the patients. 5,6 Several genes located on chromosome 3p have been studied in HCC as well as CC and include RASSF1A on 3p21.31, FHIT at 3p14.2, RIZ1, VHL at 3p25. 7-10 These results directed an intensive search for possible tumor suppressor genes located in the 3p21 region for one or more genes that could function as gatekeepers in molecular pathogenesis of human cancers. A group of candidate tumor suppressor genes (designated BLU, SEMAPHORIN 3B, or RASSF1A) has recently been mapped to this critical gene-rich region. 2,[11][12][13] SEMAPHORIN 3B (SEMA3B) is a member of the semaphorin family, which is also located on 3p21.3. Semaphorins are a family of signaling molecules initially identified to play a role in axonal guidance and can be classified as either membrane-bound (classes 1, 4, 5 and 6) or secreted (classes 2 and 3). 14 The receptors for the class 3 semaphorins are also known as neuropilin receptors. The intr...

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Section: Discussionmentioning

confidence: 99%

Section: Methylation Analysismentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Allele loss and epigenetic inactivation of 3p21.3 in malignant liver tumors

Tischoff

Markwarth

Witzigmann

et al. 2005

Intl Journal of Cancer

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“…62 The sequences of these genes indicated that the proteins they encoded were two additional members of the human semaphorin family, semaphorin 3B and 3F, belonging to class 3 semaphorins, whose receptors are the neuropilins. Following this report, SEMA3B was observed to be hypermethylated in lung cancers, and several point mutations were identified along with loss of heterozygosity (LOH) in the region.…”

Section: Life or Death: Another Pathway For The P53 Switchmentioning

confidence: 99%

p53, apoptosis and axon-guidance molecules

Arakawa¹

2005

Cell Death Differ

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The p53 tumor-suppressor gene regulates apoptosis through the transcriptional activation of its target genes. The expression of the axon-guidance molecule UNC5B (also designated p53RDL1), which is a receptor for netrin-1, is directly regulated by p53. In the absence of netrin-1, UNC5B mediates p53-dependent apoptosis. Conversely, in the presence of netrin-1, p53-induced apoptosis is inhibited through the signaling pathway activated by the interaction between netrin-1 and UNC5B. A number of other molecules that are involved in axon guidance are inactivated in human cancers and are also regulated by p53. These findings suggest a close link between axon-guidance molecules and tumorigenesis.

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Analysis of a zebrafish semaphorin reveals potential functions in vivo

et al. 1999

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The semaphorin/collapsin gene family is a large and diverse family encoding both secreted and transmembrane proteins, some of which are thought to act as repulsive axon guidance molecules. However, the function of most semaphorins is still unknown. We have cloned and characterized several semaphorins in the zebrafish in order to assess their in vivo function. Zebrafish semaZ2 is expressed in a dynamic and restricted pattern during the period of axon outgrowth that indicates potential roles in the guidance of several axon pathways. Analysis of mutant zebrafish with reduced semaZ2 expression reveals axon pathfinding errors that implicate SemaZ2 in normal guidance.

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Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns.

Cited by 216 publications

References 26 publications

Allele loss and epigenetic inactivation of 3p21.3 in malignant liver tumors

Allele loss and epigenetic inactivation of 3p21.3 in malignant liver tumors

p53, apoptosis and axon-guidance molecules

Analysis of a zebrafish semaphorin reveals potential functions in vivo

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