Physical and transcript map of the region between D6S264 and D6S149 on chromosome 6q27, the minimal region of allele loss in sporadic epithelial ovarian cancer

Liu, Ying; Emilion, G; Mungall, Andrew J.; Dunham, Ian; Beck, Stephan; Meuth-Metzinger, Valerie G Le; Shelling, Andrew N.; Charnock, F. Mark L.; Ganesan, Trivadi S.

doi:10.1038/sj.onc.1205067

Cited by 24 publications

(31 citation statements)

References 44 publications

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“…In contrast, in the same cell line, RNASE6PL, located telomeric to RPS6KA2, did not have any effect. We have confirmed this in other cell lines (Liu et al, 2002b). To perform short-term experiments where the levels of expression of RPS6KA2 are high, we chose the adenoviral system, which has been used for other genes (Schreiber et al, 1999).…”

Section: Discussionmentioning

confidence: 69%

“…The other candidate proposed as a class II tumour suppressor gene is the extracellular ribonuclease RNASE6PL (Trubia et al, 1997;Acquati et al, 2001), which is the nearest gene telomeric to RPS6KA2 and maps distally to markers D6S193 and D6S297. We have examined this possibility and we were unable to confirm that it is a tumour suppressor gene (Liu et al, 2002b).…”

Section: Discussionmentioning

confidence: 89%

“…Initially, a minimal region of allele loss was delineated between D6S193 and D6S149 (1.9 cM, 0.6 Mb) on chromosome 6q based on one tumour (Saito et al, 1992). We showed previously that the minimal region of allele loss was between D6S297 and D6S264 (3 cM, 0.6 Mb) based on analysis of 56 ovarian tumours (Cooke et al, 1996a, b;Liu et al, 2002b). The maximal frequency of allele loss occurred at D6S193 (62%) and D6S297 (52%), which are 55 kb apart.…”

Section: Introductionmentioning

confidence: 85%

“…We had previously mapped a region of allele loss between D6S264 and D6S149 at chromosome 6q27 in sporadic ovarian cancer (Cooke et al, 1996a, b;Liu et al, 2002b). The order of the genes located between D6S264 and D6S149 (1.2 Mb) is D6S264-RPS6KA2-D6S193-D6S297-RNASE6PL-FOP-CCR6-GPR31-TCP 10-UNC93-D6S149.…”

Section: Mapping Of Rps6ka2 At 6q27mentioning

confidence: 99%

“…Ovarian cancer cell line Northern blot was prepared from mRNA from cell lines as described (Liu et al, 2002b). Both blots were hybridized to full-length RPS6KA2 cDNA as described (Liu et al, 2002b).…”

Section: Northern Blotsmentioning

confidence: 99%

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RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

et al. 2006

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We had previously defined by allele loss studies a minimal region at 6q27 (between D6S264 and D6S297) to contain a putative tumour suppressor gene. The p90 ribosomal S6 kinase-3 gene (p90 Rsk-3, RPS6KA2) maps in this interval. It is a serine-threonine kinase that signals downstream of the mitogen-activated protein kinase pathway. It is expressed in normal ovarian epithelium, whereas reduced or absent in tumours or cell lines. We show that RPS6KA2 is monoallelically expressed in the ovary suggesting that loss of a single expressed allele is sufficient to cause complete loss of expression in cancer cells. Further, we have identified two new isoforms of RPS6KA2 with an alternative start codon. Homozygous deletions were identified within the RPS6KA2 gene in two cell lines. Re-expression of RPS6KA2 in ovarian cancer cell lines suppressed colony formation. In UCI101 cells, the expression of RPS6KA2 reduced proliferation, caused G1 arrest, increased apoptosis, reduced levels of phosphorylated extracellular signal-regulated kinase and altered other cell cycle proteins. In contrast, small interfering RNA against RPS6KA2 showed the opposite effect in 41M cells. The above results suggest that RPS6KA2 is a putative tumour suppressor gene to explain allele loss at 6q27.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 85%

Section: Mapping Of Rps6ka2 At 6q27mentioning

confidence: 99%

Section: Northern Blotsmentioning

confidence: 99%

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RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

et al. 2006

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A recombinant human RNASET2 glycoprotein with antitumorigenic and antiangiogenic characteristics

Smirnoff

Roiz

Angelkovitch

et al. 2006

Cancer

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Objectives: Diets consisting of diverse food items provide a wide range of nutrients that can enhance nutritional quality of the diet. Few studies have, however, assessed dietary diversity and its effects on micronutrient health in rural populations in field settings. This study assesses how well Dietary Diversity Score (DDS), an indicator of dietary diversity based on a simple count of food groups consumed, predicts the micronutrient status, focusing on serum vitamin A concentration. Methods: We used cross‐sectional data from women in food‐insecure northern Kenya where dietary diversity is likely critical for micronutrient health yet under‐studied. A linear regression model was applied to examine the relationships between DDS and serum retinol concentration. A logistic regression model was used to test DDS as a predictor of vitamin A insufficiency (serum retinol < 1.05 μmol/l). Results: DDS had a significant positive effect on serum retinol concentration (t = 2.01, P = 0.045) after adjusting for age, wealth, acute phase reaction, hemoglobin, vitamin A intake and vitamin A supplementation. A one unit increase in DDS by adding an extra food group in one's diet was significantly less likely to have vitamin A insufficiency (OR = 0.64, P = 0.026) after adjusting for the covariates. Conclusions: Our results indicate that diversified diets enhance vitamin A status relative to narrower diets with equivalent vitamin A content. DDS shows a potential as a low‐cost, field‐friendly method for exploratory assessments of vitamin A status, and a potential as a research tool for human biologists and anthropologists interested in dietary quality and micronutrient health. Am. J. Hum. Biol., 2012. © 2012 Wiley Periodicals, Inc.

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Identification of candidate tumor‐suppressor genes in 6q27 by combined deletion mapping and electronic expression profiling in lymphoid neoplasms

Steinemann

Gesk

Zhang

et al. 2003

Genes Chromosomes & Cancer

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Deletions in the long arm of chromosome 6 (6q) are among the most frequent chromosome aberrations in lymphoid neoplasms. Recently, the region of minimal deletion (RMD1) in 6q27 was narrowed down to 5-9 Mb. In the present study, we aimed to define the distal border of the commonly lost region in 6q27 more precisely and to identify and investigate tumor-suppressor genes (TSGs) from this region. Twenty-nine cases, in which our previous fluorescence in situ hybridization (FISH) screening that used a set of 36 YAC probes revealed loss in 6q25-27, were further investigated by means of FISH. In all cases, deletions of 6q27 extended from yeast artificial chromosome (YAC) 977e10 spanning the proximal border of RMD1 to the most telomeric YAC 933f7 within the recently established YAC-contig of this region. An interstitial homozygous deletion, flanked by the telomeric probe TelVysion6q and YAC 971g12, was detected, which substantially narrows down the RMD1. To identify candidate TSGs down-regulated in malignant lymphomas from this region of homozygous loss, we performed electronic profiling of expressed sequences mapped to this region. This analysis suggested the gene PDCD2 originally thought to be involved in programmed cell death to be probably down-regulated in malignant B-cell lymphomas compared to normal B lymphocytes. Nevertheless, mutation analyses failed to identify mutations in the coding region of PDCD2 in nine lymphomas with FISH-proved 6q27 deletions. Furthermore, epigenetic studies in these nine and an additional 48 lymphomas did not show altered methylation of the PDCD2 locus in these tumors. Possibly haploinsufficiency is effectual in accelerating tumor progression.

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Physical and transcript map of the region between D6S264 and D6S149 on chromosome 6q27, the minimal region of allele loss in sporadic epithelial ovarian cancer

Cited by 24 publications

References 44 publications

RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

A recombinant human RNASET2 glycoprotein with antitumorigenic and antiangiogenic characteristics

Identification of candidate tumor‐suppressor genes in 6q27 by combined deletion mapping and electronic expression profiling in lymphoid neoplasms

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