Fine mapping of the 1q21 breakpoint of the papillary venal cell carcinoma-associated (X;1) translocation

A combination of Southern blot analysis on a panel of tumor-derived somatic cell hybrids and fluorescence in situ hybridization (FISH) techniques was used to map a series of DNA markers relative to the 1q21 breakpoint of the renal cell carcinoma (RCC)-associated (X;1)-(p11;q21) translocation. This breakpoint maps between several members of the S100 family which are clustered in the 1q21 region and a conserved region between man and mouse containing the markers SPTA1-CRP-APCS-FcER1A-ATP1A2-APOA2. The location of the breakpoint coincides with the transition of a region of synteny of human chromosome 1 with mouse chromosomes 3 and 1

UNIPARENTAL ORIGIN OF I(12P) IN HUMAN GERM-CELL TUMORS

We present molecular data to demonstrate that the isochromosome 12p, specific for human germ cell tumors (GCTs), is of uniparental origin. Eight GCT-derived cell lines, containing one or more copies of i(12p) and/or other 12p anomalies, were analyzed with different 12p-derived polymorphic markers. The results from Ma-90, a near-diploid cell line with only one i(12p) in addition to two copies of a normal chromosome 12, clearly show an allelic 12p ratio of approximately 3:1, indicating that both 12p arms are of identical parental origin. These results were further substantiated by data obtained from the other i(12p)-positive GCT-derived cell lines. Therefore, we conclude that the i(12p) in GCTs constitutes a genuine isochromosome with genetically identical arms. The isochromosome most likely originates from a misdivision of the centromere rather than from a translocation or a non-sister chromatid exchange as proposed by others. We also found that supernumerary 12p copies, as observed in i(12p)-negative GCTs, are of uniparental origin. These observations seem to point to an important role for certain 12p-derived sequences in the development of human GCTs

Fluorescence in situ hybridization-based approaches for detection of 12p overrepresentation, in particular i(12p), in cell lines of human testicular germ cell tumors of adults

Overrepresentation of the short arm of chromosome 12 is frequently detected in human testicular germ cell tumors of adolescents and adults (TGCT). This overrepresentation mostly results from the formation of an isochromosome: i(12p). Whether the overrepresentation consistently involves the complete 12p arm including the centromere is still unclear. We studied five TGCT-derived cell lines (NT2, 2102Ep, H12.1, NCCIT, and S2), combining conventional chromosome banding, fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH) to investigate the suitability of each of these techniques to detect aberrations involving chromosome 12. Karyotyping showed one or more i(12p)s in NT2, 2102Ep, H12.1, and S2. However, FISH with a centromere-specific probe (p alpha 12J8), a 12p ''paint'' and a 12p11.2-12.1 region-specific probe yeast artificial chromosome (YAG)#5 and CGH could not confirm the presence of an i(12p) in S2. Additional randomly distributed 12p sequences were detected by FISH in H12.1, NCCIT, and S2. In most of these cases, (a part of) of the centromere was included. All overrepresented 12p regions, except for those in S2, showed hybridization with YAC#5. CGH showed increased copy numbers of the complete 12p arm in the cell lines with one or more i(12p)s but no overrepresentation was noted in the cell lines without i(12p). In metaphase spreads, the centromeric block of the i(12p)s differed in size as compared with those of normal chromosomes 12. This was rarely noted in interphase nuclei. A decrease in size of the centromeric block in 2102Ep and H12.1 caused a weak FISH signal, which was difficult to detect, especially in interphase nuclei. The ratio between p alpha 12H8- and YAC#5-derived signals reflected the presence or absence of one or more i(12p)s. Our results indicate that double FISH with a centromere- and a 12p-specific probe can be used to detect 12p ovrrepresentation [including i(12p)] in TGCT both in metaphase spreads and interphase nuclei. CGH confirmed the relative overrepresentation of 12p sequences as detected by FISH and showed that in these cell lines the complete 12p was involved

Clondalkin Drug Task Force strategic plan 2008.

Clondalkin Drugs Task Force: The Clondalkin Drug Task Force is one of 14 LDTFs located mainly in the greater Dublin region. Their overall role is to prepare and implement action plans which identify existing and emerging gaps in services in relation to education/prevention, treatment, rehabilitation and curbing local supply. To date the Clondalkin Drug Task Force The Task Forces has drawn up two Area Actions Plans based on intensive consultations (1997/8 and 2001). The plans represent a consensus on the priority issues to be addressed in the community in terms of problematic drug use. Each plan included a range of measures in terms of treatment, rehabilitation, education and prevention, and curbing the local supply of drugs. The initial Action Plan focused on education and prevention strategies and actions in response to the identified need for innovative community based education programmes in Clondalkin. CDTF’s most recent Area Action Plan was developed in 2001 and entitled ‘Making Progress’. In the development of the this Action Plan, the Task Force reflected on the lessons learned from implementing the initial plan and developed a number of strategies and actions that focused on Treatment & Rehabilitation. Prevalence of Drug Problems in Clondalkin: The research shows that drug use in Clondalkin is perceived to have become more problematic. The prevalence survey suggested that there are greater quantities and varieties of drugs available and there has been an increase in the proportion of younger people using drugs than was the case in the past. The respondents to the survey feel that drug dealing has become more visible in the locality. Drug consumption mostly occurs in the user’s place of residence and the first encounter with illicit drugs typically occurred in the company of friends. Heroin is the overwhelming primary problematic drug of use. Yet, there has been a notable increase in the problematic use of cocaine, alcohol and prescription drugs. Cocaine has become a frequently used recreational drug in Clondalkin. There is some indication in the survey that crack cocaine is an emerging problem drug. The survey highlights how polydrug use is the norm. There are a wide variety of polydrug use patterns: heroin combined with either cannabis, cocaine, benzodiazepines, alcohol or crack cocaine, are the most common patterns of use. The typical pattern for recreational drug users was cocaine combined with either cannabis or alcohol. The injection of cocaine by injecting heroin users was another emerging trend. This research suggests there are 1,591 opiate users in the area. Heroin was overwhelmingly the main problem drug for this cohort. The typical problematic drug user (especially opiates) in Clondalkin is most commonly a male, Irish, single, unemployed, early school leaver between the ages of 15 and 24 years. The MQI research indicates that in contrast to heroin users, recreational cocaine users come from all age groups and all social strata. The majority of problem drug users do not seek treatment until their late twenties and early thirties. This research suggests that there is an obvious lack of data available on drug use among ethnic minorities. This emerges through the lack of engagement by those from new communities with existing treatment services and also lack of general knowledge on the part of community and statutory services of the profile of new communities in Clondalkin. This report reveals that the causes of drug problems were perceived as wide, differed depending on the respondent’s relationship with drugs and ranged across a number of factors such as contact with problematic drug use; family dysfunction; lack of education, low self-esteem and peer influences; curiosity, adolescent experimentation and an awareness of the pleasurable aspects of drug use. Hepatitis C is quite prevalent among Injecting Drug Users (IDUs) according to the survey. In addition, one fifth of those interviewed had been diagnosed with a psychiatric illness and have accessed mental health services. A significant minority of IDUs reported not being aware of needle exchange services in Clondalkin. MQI also show that there was a marginal decrease in the numbers of individuals accessing drug treatment services over the three year period, 2004-2007. It is perceived that services have improved over the past 5 years, due to the increase of facilities. Criticisms of current services included the lack of a ‘moving on’ or progression mechanism as well as the lack of input of clients to their drug treatment. There was widespread agreement that there is a lack of drug treatment services in the Clondalkin area and insufficient numbers of detoxification programmes available. The research also suggests that there is a clear need for a local homeless service in order to provide suitable facilities for homeless drug users. There was a perception that drug related violence has increased significantly in recent years. There was a notable increase in simple possession and possession for sale and supply incidents from 2005 to 2006. Participants in the research perceived that there is a lack of Garda personnel dedicated to tackling drug related crime in Clondalkin. The effects of drug problems on families include: physical and psychological stress; financial burden of payment of drug debts; grandparents who are taking care of their grandchildren; and, concerns for children of drug users in relation to their early exposure to drug addiction. The effects of drug problems on the community include: the crime element of drug use and the openness of dealing; fear of using public amenities; and that community anti-drug activism appears to have diminished due to fatigue