Expression of ras oncogene p21 protein in normal and neoplastic laryngeal tissues: correlation with histopathological features and epidermal growth factor receptors.

Western blotting analysis of the p21 ras oncoprotein was performed in seven normal laryngeal mucosa specimens and 43 primary laryngeal cancers. Varying p21 levels, expressed as optical density (OD), were found in normal mucosa (median 1.94 OD, range 0.90-2.17 OD) and in primary laryngeal tumours (median 1.74 OD, range 0.30-6.37 OD). When p21 expression in laryngeal cancer was compared with the normal counterpart, higher levels were found in neoplastic than in normal laryngeal tissue (median 2.54 OD, range 1.76-6.37 OD, vs median 1.94 OD, range 0.90-2.17 OD) (P = 0.023). Immunohistochemical analysis demonstrated that most of the tumour cells (more than 70%) were immunostained while the stromal component was unreactive. No correlation between p21 expression and tumour location, stage and histopathological grade was observed. The correlation between ras p21 protein expression and epidermal growth factor receptor (EGFR) levels was also investigated. EGFR-positive cases did not show any difference in p21 expression with respect to EGFR-negative cases (median 1.52 OD, range 0.30-6.37 OD, vs median 1.84 OD, range 0.93-3.71 OD). Our findings suggest that overexpression of p21 protein is associated with a malignant phenotype in laryngeal cancer. Further studies should be undertaken to evaluate whether the assessment of p21 protein expression may have clinical significance in laryngeal cancer

Tempered mlo broad-spectrum resistance to barley powdery mildew in an Ethiopian landrace

Recessive mutations in the Mlo gene confer broad spectrum resistance in barley (Hordeum vulgare) to powdery mildew (Blumeria graminis f. sp. hordei), a widespread and damaging disease. However, all alleles discovered to date also display deleterious pleiotropic effects, including the naturally occurring mlo-11 mutant which is widely deployed in Europe. Recessive resistance was discovered in Eth295, an Ethiopian landrace, which was developmentally controlled and quantitative without spontaneous cell wall appositions or extensive necrosis and loss of photosynthetic tissue. This resistance is determined by two copies of the mlo-11 repeat units, that occur upstream to the wild-type Mlo gene, compared to 11-12 in commonly grown cultivars and was designated mlo-11 (cnv2). mlo-11 repeat unit copy number-dependent DNA methylation corresponded with cytological and macroscopic phenotypic differences between copy number variants. Sequence data indicated mlo-11 (cnv2) formed via recombination between progenitor mlo-11 repeat units and the 3' end of an adjacent stowaway MITE containing region. mlo-11 (cnv2) is the only example of a moderated mlo variant discovered to date and may have arisen by natural selection against the deleterious effects of the progenitor mlo-11 repeat unit configuration

Vascular endothelial growth factor in node-positive breast cancer patients treated with adjuvant tamoxifen

In 212 postmenopausal women with node-positive oestrogen receptor-positive (ER(LBA)) breast cancer subjected to radical surgery and adjuvant tamoxifen, the risk of 6-year relapse increased with increasing values of intratumoral vascular endothelial growth factor (VEGF) in patients whose tumours had a low/intermediate ER(LBA) content compared to patients with high-ER(LBA) tumours. These findings indicate that tumour progression, activated or sustained by high VEGF levels, may be counteracted in high-ER(LBA) cancers by tamoxifen, which in contrast fails to contrast the metastatic potential in low-ER(LBA) tumours

A saturated SSR/DArT linkage map of Musa acuminata addressing genome rearrangements among bananas

Background: The genus Musa is a large species complex which includes cultivars at diploid and triploid levels. These sterile and vegetatively propagated cultivars are based on the A genome from Musa acuminata, exclusively for sweet bananas such as Cavendish, or associated with the B genome (Musa balbisiana) in cooking bananas such as Plantain varieties. In M. acuminata cultivars, structural heterozygosity is thought to be one of the main causes of sterility, which is essential for obtaining seedless fruits but hampers breeding. Only partial genetic maps are presently available due to chromosomal rearrangements within the parents of the mapping populations. This causes large segregation distortions inducing pseudo-linkages and difficulties in ordering markers in the linkage groups. The present study aims at producing a saturated linkage map of M. acuminata, taking into account hypotheses on the structural heterozygosity of the parents. Results: An F1 progeny of 180 individuals was obtained from a cross between two genetically distant accessions of M. acuminata, 'Borneo' and 'Pisang Lilin' (P. Lilin). Based on the gametic recombination of each parent, two parental maps composed of SSR and DArT markers were established. A significant proportion of the markers (21.7%) deviated (p < 0.05) from the expected Mendelian ratios. These skewed markers were distributed in different linkage groups for each parent. To solve some complex ordering of the markers on linkage groups, we associated tools such as tree-like graphic representations, recombination frequency statistics and cytogenetical studies to identify structural rearrangements and build parsimonious linkage group order. An illustration of such an approach is given for the P. Lilin parent. Conclusions: We propose a synthetic map with 11 linkage groups containing 489 markers (167 SSRs and 322 DArTs) covering 1197 cM. This first saturated map is proposed as a "reference Musa map" for further analyses. We also propose two complete parental maps with interpretations of structural rearrangements localized on the linkage groups. The structural heterozygosity in P. Lilin is hypothesized to result from a duplication likely accompanied by an inversion on another chromosome. This paper also illustrates a methodological approach, transferable to other species, to investigate the mapping of structural rearrangements and determine their consequences on marker segregation. (Résumé d'auteur

Development of expressed sequence tag and expressed sequence tag-simple sequence repeat marker resources for Musa acuminata.

Banana (Musa acuminata) is a crop contributing to global food security. Many varieties lack resistance to biotic stresses, due to sterility and narrow genetic background. The objective of this study was to develop an expressed sequence tag (EST) database of transcripts expressed during compatible and incompatible banana-Mycosphaerella fijiensis (Mf) interactions. Black leaf streak disease (BLSD), caused by Mf, is a destructive disease of banana. Microsatellite markers were developed as a resource for crop improvement

Oryza Tag Line, a phenotypic mutant database for the Génoplante rice insertion line library

To organize data resulting from the phenotypic characterization of a library of 30 000 T-DNA enhancer trap (ET) insertion lines of rice (Oryza sativa L cv. Nipponbare), we developed the Oryza Tag Line (OTL) database (http://urgi.versailles.inra.fr/OryzaTagLine/). OTL structure facilitates forward genetic search for specific phenotypes, putatively resulting from gene disruption, and/or for GUSA or GFP reporter gene expression patterns, reflecting ET-mediated endogenous gene detection. In the latest version, OTL gathers the detailed morpho-physiological alterations observed during field evaluation and specific screens in a first set of 13 928 lines. Detection of GUS or GFP activity in specific organ/tissues in a subset of the library is also provided. Search in OTL can be achieved through trait ontology category, organ and/or developmental stage, keywords, expression of reporter gene in specific organ/tissue as well as line identification number. OTL now contains the description of 9721 mutant phenotypic traits observed in 2636 lines and 1234 GUS or GFP expression patterns. Each insertion line is documented through a generic passport data including production records, seed stocks and FST information. 8004 and 6101 of the 13 928 lines are characterized by at least one T-DNA and one Tos17 FST, respectively that OTL links to the rice genome browser OryGenesDB

Genome-wide analysis of japonica rice performance under limited water and permanent flooding conditions

A rice GWAS panel of 281 accessions of japonica rice was phenotypically characterized for 26 traits related to phenology, plant and seed morphology, physiology and yield for 2 years in field conditions under permanent flooding (PF) and limited water (LW). A genome-wide analysis uncovered a total of 160 significant marker-trait associations (MTAs), of which 32 were LW-specific, 59 were PF-specific, and 69 were in common between the two water management systems. LW-specific associations were identified for several agronomic traits including days to maturation, days from flowering to maturation, leaf traits, plant height, panicle and seed traits, hundred grain weight, yield and tillering. Significant MTAs were detected across all the 12 rice chromosomes, while clusters of effects influencing different traits under LW or in both watering conditions were, respectively, observed on chromosomes 4, 8, and 12 and on chromosomes 1, 3, 4, 5, and 8. The analysis of genes annotated in the Nipponbare reference sequence and included in the regions associated to traits related to plant morphology, grain yield, and physiological parameters allowed the identification of genes that were demonstrated to affect the respective traits. Among these, three (OsOFP2, Dlf1, OsMADS56) and seven (SUI1, Sd1, OsCOL4, Nal1, OsphyB, GW5, Ehd1) candidate genes were, respectively, identified to co-localize with LW-specific associations and associations in common between the two water treatments. For several LW-specific MTAs, or in common among the two treatments, positional co-localizations with previously identified QTLs for rice adaptation to water shortages were observed, a result that further supports the role of the loci identified in this work in conferring adaptation to LW. The most robust associations identified here could represent suitable targets for genomic selection approaches to improve yield-related traits under LW

Infiltrating ductal and lobular breast carcinomas are characterised by different interrelationships among markers related to angiogenesis and hormone dependence

To obtain a more integrated understanding of the different breast cancer phenotypes and to investigate whether bio-molecular profiles can distinguish between specific histotypes, we explored the interrelations among several biologic variables indicative of, or related to, hormone dependence, proliferation and apoptosis control, and angiogenesis in ductal and lobular carcinomas, the most common histotypes. Oestrogen and progesterone receptors, tumour proliferative activity, the expression of cyclin A, p16ink4A, p27kip1, p21waf1, p53, bcl-2, and levels of vascular endothelial growth factor and hypoxia-inducible factor-1α (HIF-1α) were evaluated in 190 in ductal and 67 lobular carcinomas. Our findings support the hypothesis that in ductal and lobular carcinomas are two distinct, partially phenotypically unrelated entities, the latter being characterised by the presence of features indicative of differentiation such as oestrogen receptors, low proliferation and lack of p53 expression and associated with low vascular endothelial growth factor content compared to angiogenesis in ductal carcinomas. Conversely, no significant difference was found between lobular carcinomas and in ductal carcinomas considering the frequency distribution of PgR-positive cases, cyclin-dependent kinase inhibitors acting at the G1/S boundary, bcl-2 and HIF-1α protein expression. Although both generally defined as hormone responsive, in ductal and lobular carcinomas are also characterised by biologic patterns in which proteins related to hormone responsiveness, cell-cycle control, apoptosis and angiogenesis were differently associated. This finding suggests the need to refine breast cancer characterisation in order to provide detailed information about individual tumours, or subsets of tumours, that will help in defining optimal treatment approaches