Cytogenetic and fluorescence in situ hybridization analyses of chromosome 19 aberrations in pancreatic carcinomas: Frequent loss of 19p13.3 and gain of 19q13.1-13.2

Höglund, Mattias; Gorunova, Ludmila; Andrén‐Sandberg, Åke; Dawiskiba, Sigmund; Mitelman, Felix; Johansson, Bertil

doi:10.1002/(sici)1098-2264(199801)21:1<8::aid-gcc3>3.0.co;2-5

Cited by 50 publications

(29 citation statements)

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“…We analysed the mechanism by which GNG7 expression was reduced in oesophageal cancer. Loss of chromosome 19p13.3, which includes the GNG7 locus, has been observed frequently in several cancers (Ritland et al, 1995;Hoglund et al, 1998;Wang et al, 1999;Kato et al, 2004;Miyai et al, 2004;Yang et al, 2004). Furthermore, STK11, the Peutz -Jeghers gene, is also located on the telomeric region of chromosome 19p13.3 (Hemminki et al, 1998;Jenne et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer

et al. 2008

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We previously cloned human G protein gamma 7 (GNG7) and demonstrated that it was downregulated in gastrointestinal cancer. The significance of GNG7 expression in oesophageal cancer is unknown. TaqMan quantitative real-time PCR was performed to determine the clinical significance of GNG7 expression in 55 cases of oesophageal cancer. Furthermore, GNG7-transfected oesophageal cancer cells were analysed in laboratory studies at genomic and epigenetic levels. Twenty-seven patients with low GNG7 expression showed significantly poorer survival than did 28 patients with high expression (Po0.05). Tumours with low GNG7 expression invaded deeper than those with high GNG7 expression (Po0.05), both in vivo and in vitro. Eight tumours retained GNG7 expression, and they did not show either promoter hypermethylation or loss of heterozygosity (LOH). In 38 tumours with GNG7 suppression, 22 (57%) showed either LOH or promoter hypermethylation. In addition, GNG7 expression was significantly associated with the presence of miR328 in oesophageal cancer cell lines, which suggests that this microRNA might be a regulator of GNG7 expression. GNG7 suppression represents a new prognostic indicator in cases of oesophageal cancer. GNG7 might be suppressed by LOH and promoter hypermethylation or by microRNA.

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Section: Discussionmentioning

confidence: 99%

Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer

et al. 2008

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“…Third, although it was reported that there was no detectable interaction between p34 SEI-1 and cyclin D1 (18), the existence of a cyclin A-binding motif ( Figure 1) (19) provides p34 SEI-1 the potential to interact with cyclins, thus indirectly affecting CDKs. Last, amplification of p34 SEI-1 gene is a common event in human cancers such as ovarian tumors (20) and pancreatic tumors (21)(22)(23), in which p16 gene is inactivated or expressed at very low levels (24). If p34 SEI-1 is indeed oncogenic, it is unclear how or whether this is caused solely by counteracting the CDK4-inhibitory activity of p16.…”

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confidence: 99%

The Nuclear Protein p34^SEI^-¹ Regulates the Kinase Activity of Cyclin-Dependent Kinase 4 in a Concentration-Dependent Manner

2004

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Previous studies have shown that p34 SEI-1 , also known as TRIP-Br1, is involved in cell cycle regulations by interacting with a number of important proteins including CDK4. However, the detailed mechanism and structural basis of the interaction remains to be determined. We report the use of in vitro studies to address these problems. First, it was shown that p34 SEI-1 binds to CDK4 directly, and the binding does not compete directly with p16. In the presence of p16, a quaternary complex is formed between p34 SEI-1 , CDK4, cyclin D2, and p16. Second, it was found that p34 SEI-1 activates the kinase activity of CDK4 at lower concentrations (reaching the maximum at 500 nM) but inhibits the same activity at higher concentrations, implying that p34 SEI-1 -mediated CDK4 activation is dose-dependent. Again, the effects of p34 SEI-1 and p16 are independent of each other. Third, it was shown that p34 SEI-1 possesses a LexA-mediated transactivation activity. Finally, a set of truncation mutants were used to dissect the structural elements responsible for the different functions of p34 SEI-1 . The results indicate that the fragment 30-160 can bind, activate, and inhibit CDK4; the fragment 30-132 can bind and activate but does not inhibit CDK4, while the fragment 30-88 cannot bind, activate, or inhibit but retains the LexA-mediated transactivation activity.Mammalian cyclin-dependent kinases (hereafter, CDKs) 1 are a group of conserved serine/threonine protein kinases driving the cell through most of the major cell cycle control points (1-3). In conjunction with different cyclins, CDKs phosphorylate specific substrates, which subsequently turn on/off downstream genes required for cell progression (4). For instance CDK4 and 6, in partnership with D cyclins, specifically phosphorylate the retinobalstoma susceptible gene product (Rb), thus regulating entry into the cell cycle and passage through the checkpoint in late G1 (2). As the central molecules of the machinery controlling cell progression, all CDKs are strictly controlled by multiple mechanisms, such as gene amplification and transcription, holoenzyme assembly, posttranslational modification, and protein/ protein interactions (5). Many proteins have been found to act as negative or positive kinase regulators of CDK4 and 6 through protein/protein interactions. While binding of D cyclins is required for the full kinase activity (4), INK4 (including p16, p15, p18, and p19) (6-11) and KIP (including p21, p27, and p57) proteins (5,(12)(13)(14) are inhibitors of CDK4 and 6. Moreover, the oncoprotein Tax from human T-cell leukemia virus 1 (HTLV-1) stimulates the CDK4 activity in infected cells through physical association (15,16), and the oncoprotein gankyrin affects CDK4 by counteracting against the inhibition of p16 and p18 (17). The intricate regulation of CDK4 and 6 activitied by these and possibly many other proteins is crucial for cell cycling and tumorigenesis.p34 SEI-1 , a nuclear protein originally cloned through a yeast two-hybrid approach using human p16 a...

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“…The YAC map given on the right side of the ideogram is based on the map published by Giacalone et al (1996), except for 955c2 (Bray-Ward et al, 1996). YAC probe preparations were performed as in Lengauer et al (1992), using Alu primers described in Hoglund et al (1998). Probes were labelled with either biotin or digoxygenin-conjugated dUTP, using Amersham's Mega Prime kit (Amersham, UK).…”

Section: Probes and Fish Analysismentioning

confidence: 99%

“…After labelling, the DNA was purified on a Sepharose CL-6B column (Pharmacia, Uppsala, Sweden). The FISH analyses were performed essentially as described in Hoglund et al (1998). The hybridization signals were analysed in a CytoVision Ultra system (Applied Imaging, Sunderland, UK), using a charged coupled device (CCD) camera.…”

Section: Probes and Fish Analysismentioning

confidence: 99%

Cytogenetic and FISH analyses of pancreatic carcinoma reveal breaks in 18q11 with consistent loss of 18q12-qter and frequent gain of 18p

Höglund

Gorunova²,

Jonson³

et al. 1998

Br J Cancer

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Summary Chromosome 18 was analysed using a banding technique and fluorescence in situ hybridization (FISH) in 13 pancreatic carcinoma samples. The cytogenetic analysis revealed that chromosome 18 abnormalities were present in all cases and that several different rearrangements, such as translocations, deletions, dicentrics and ring chromosomes, were often found together. FISH mapping using 18q YAC probes showed that all tumours had lost at least one copy of 1 8q and that 1 8p was over-represented in 6 of the 13 cases. Furthermore, out of 13 identified deletion breakpoints on 18q, 11 were mapped to 18q11. The clustering of breaks close to the centromere indicates that loss of genes in bands 18q11 and 18q12, in addition to those located in 18q21, e.g. DPC4 and DCC, are important in the development of pancreatic tumours.Keywords: chromosome 18; pancreatic carcinoma; deletions Although only a handful of larger series of cytogenetically investigated pancreatic carcinomas have been reported, several frequent recurrent chromosomal imbalances, such as trisomy 7 and 20, monosomy 18, loss of Ip, 3p, 6q, 8p, 9p, 17p and 19p, and gain of lq, 3q, 8q, 1 lq, 19q and 20q, have been identified (Johansson et al, 1992;Bardi et al, 1993;Griffin et al, 1994Griffin et al, , 1995Gorunova et al, 1998). The pattern of cytogenetic imbalances seems characteristic for pancreatic cancer, albeit many of the individual changes are also found in other solid tumours (Mertens et al, 1997). Loss of heterozygosity (LOH) studies have confirmed the cytogenetic features in pancreatic tumours as regards losses, showing a high incidence of allelic imbalance at lp, 3p, 9p, 13q, 17p and 18q Hahn et al, 1995;Shridhar et al, 1996). In some of the frequently deleted regions, a concomitant inactivation of a tumour-suppressor gene (TSG) on the remaining normal chromosome has been shown, i.e. CDKN2A in 9p2l Bartsch et al, 1995), BRCA2 in 13q12 (Goggins et al, 1996), TP53 in 17pl3 (Ruggeri et al, 1992;Scarpa et al, 1993) and SMAD4 (DPC4) in 18q21 , whereas the TSGs in the other loci remain to be identified.The most common chromosome aberration in pancreatic cancer is monosomy 18 (Johansson et al, 1992;Bardi et al, 1993;Griffin et al, 1994Griffin et al, , 1995. However, recent cytogenetic (Gorunova et al, 1998) and comparative genomic hybridization (CGH) analyses (Mahlamaki et al, 1997) have also revealed frequent partial deletions of 18q. In the majority of the cases, the CGH data indicate breaks in 18cen-q2 1, leading to loss of the distal half of 18q (Mahlamaki et al, 1997), including the genes DCC and SMAD4 (Fearon et al, 1990;Hahn et al, 1996). As a large proportion of Received 11 July 1997 Revised 14 October 1997 Accepted 16 October 1997 Correspondence to: M Hoglund these breaks are located close to the centromere, in bands 18q 11-12 (Gorunova et al, 1998), at quite a distance from DCC and SMAD4, larger deletions of 18q, including other putative TSGs, may be pathogenetically important in pancreatic carcinoma. However, cytogenetic and CGH breakpoint mapp...

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Cytogenetic and fluorescence in situ hybridization analyses of chromosome 19 aberrations in pancreatic carcinomas: Frequent loss of 19p13.3 and gain of 19q13.1-13.2

Cited by 50 publications

References 23 publications

Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer

Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer

The Nuclear Protein p34^SEI^-¹ Regulates the Kinase Activity of Cyclin-Dependent Kinase 4 in a Concentration-Dependent Manner

Cytogenetic and FISH analyses of pancreatic carcinoma reveal breaks in 18q11 with consistent loss of 18q12-qter and frequent gain of 18p

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Cytogenetic and fluorescence in situ hybridization analyses of chromosome 19 aberrations in pancreatic carcinomas: Frequent loss of 19p13.3 and gain of 19q13.1-13.2

Cited by 50 publications

References 23 publications

Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer

Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer

The Nuclear Protein p34SEI-1 Regulates the Kinase Activity of Cyclin-Dependent Kinase 4 in a Concentration-Dependent Manner

Cytogenetic and FISH analyses of pancreatic carcinoma reveal breaks in 18q11 with consistent loss of 18q12-qter and frequent gain of 18p

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Product

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The Nuclear Protein p34^SEI^-¹ Regulates the Kinase Activity of Cyclin-Dependent Kinase 4 in a Concentration-Dependent Manner