Molecular cytogenetics of solid tumors

Project Information

Grant agreement ID: B19

Start date 6 September 2000

End date 5 September 2005

Funded under

• European cooperation in the field of scientific and technical research (COST), 1971-

Total cost € 0,00

EU contribution No data

Coordinated by

N/A
Italy

Objective

A. Background

Current research on molecular cytogenetics of solid tumours is directed towards the identification of recurrent chromosomal rearrangements which breakpoints may pinpoint genome regions harbouring genes involved in the initiation and progression of different tumour types.
Although chromosomal changes associated with pathogenetic pathways are largely tumour-specific, an integrated view of the cytogenetic patterns of distinct tumours is necessary to tumour classification, environmental mutagenesis and to perceive the multifaceted role of several cancer genes lying at chromosomal breakpoints. Exchanges in the expertise that separate groups have achieved on different tumours may greatly accelerate basic research on as yet unidentified chromosomal changes in human tumours and provide guidelines for translation of genome discoveries to clinical and diagnostic applications.

Several multi-target Fluorescent In Situ Hybridization (FISH) techniques are applied to tumour nuclei and metaphases to simultaneously detect increased/decreased dosage of different chromosomes/chromosomal regions and multiple chromosome aberrations including complex markers. Comparative Genome Hybridization (CGH) techniques on slides, chips or filters accurately detect copy number abnormalities in a single analysis providing a powerful research approach for identifying new genetic abnormalities. Tissue microarray technology ("tissue chips") for molecular profiling of tumour progression makes FISH a high-throughput tool for cancer genetics.
A resource of mapped BACs for use in FISH analysis of chromosome rearrangements in human tumours has been recently generated.
An increasingly high number of breakpoint-spanning probe contigs is also being developed by investigators working on defined genome regions. Sharing of this repertoire combined to rapid communication on novel technologies may allow molecular cytogeneticists to achieve goals precluded a few years ago.

Molecular cytogenetics of solid tumours is a fast-growing field. For the most commonly investigated tumours knowledge on primary chromosome aberrations needs to be transferred to diagnostic services, while for a few other tumours identification of key chromosomal changes awaits further investigation.

Therefore we are convinced that it is particularly timely and necessary to establish a European network in order to promote contacts and exchanges of experience and approaches among laboratories involved in basic research and diagnostic services on solid tumours. This network should include groups devoted to development of new resources and technological tools, which may provide new insights into basic pathogenetic mechanisms or may improve routine investigation.
Investigators experienced on specific tumour types should compare their expertises and set up guidelines for optimization of diagnostic services. Interaction between these specialized labs and investigators or companies working on new tools and reagents is recommended to guarantee the application of the most rapid and economic procedures.

Currently the European Cytogeneticist Association (ECA) has enhanced cooperation of investigators in the field of basic and applied cytogenetics. Nevertheless contacts are restricted to a few international scientific events which are held every other year. Although these scientific programmes allow researchers to meet, they are inadequate to build up a continuous cooperation in a specific field, such as that of cytogenetics of benign and malignant solid tumours. The present COST Action aims at establishing a permanent network among outstanding groups located in different European laboratories which contribute actively to advances in the field of molecular cytogenetics of solid tumours on sides as different as that of new high resolution technologies (Multiplex FISH, CGH on arrays etc), set up of FISH probes spread over the whole genome, disclosure of novel cytogenetic markers (in neuroblastoma, breast cancer, soft tissue sarcomas, benign solid tumours) and the comprehensive catologuing of cancer breakpoints. The situation in European countries could be estimated by the contributions of the researchers coming from the Member States to relevant scientific meetings such as the First European Cytogenetics Conference (Athens, Greece, 1997), the Second European Cytogenetics Conference (Wien, Austria, 1999) in which solid tumours have been the topic of several plenary lectures and workshops fully dedicated to this topic such as the 6th European Workshop on Cytogenetics and Molecular Genetics of human solid tumours (Saarbrucken, Germany, 1998).

B. Objectives and benefits

The main objective of the Action is :

(i) to generate new FISH reagents and technologies. These are to be applied for the analysis of different tumour types with the aim of broadening our current knowledge of tumour-specific chromosomal changes associated with tumour development and progression and,

(ii) to transfer important breakthroughs into diagnostic services to improve on speed and efficiency of tests with prognostic and diagnostic value.
Monitoring tumour progression and their responses to therapeutic intervention will be very useful for identification and dissection of tumour-specific chromosomal markers.

Secondary objectives are to promote exchanges between the research groups in the following areas:
- Genome resources: development of reagents for FISH analysis to be used in both basic research and diagnosis of different solid tumours
- Molecular cytogenetic technology: development of novel FISH-derived techniques with high resolution and rapid processing times, tailored to overcome the difficulties caused by the heterogeneic nature of the tumour cell populations
- Molecular cytogenetics of solid tumours (including the major tumour types)
- Molecular cytogenetics of carcinomas
- Genetic predisposition to cancer

Since a few researchers of the previously described areas are very specialized in their individual topics, success is likely to depend upon establishing scientific complementarity and multidisciplinary research.
Participation of industrial representatives in the meetings will stimulate economic development of these scientific goals, and help to define the needs of biotech industrial development. It is also proposed to make guidelines for the diagnostics of solid tumours to be used by oncological laboratories performing routine diagnostic services.

C. Scientific programme

To reach our objectives, we propose the following activities:

- assemble and publish (on a dedicated web site) a directory of European laboratories, groups and individual researchers working on the molecular cytogenetic characterization of solid tumours for purposes of basic research or diagnostic activity. Investigators working on either the same tumours or complementary aspects of the same tumour will thus be able to establish cooperations and exchanges. Outside members will also get necessary information to communicate with the identified groups thus potentiating the European network;

- by means of the above directory and the knowledge of published and in press papers and progressed activities the management committee will set up a list of reference labs for each of the most common solid tumours. Investigators of the identified labs will be in charge of spreading information on recent key findings, relevant publications, diagnostic applications through organization of specific workshops;

- specialized groups of investigators will cooperate in setting up or updating guidelines for diagnosis of specific tumour types which will be published in the international literature together with joined studies within the network upon which they will be based;

- set up a working group for genomic resources and their application in solid tumour cytogenetics

- set up a working group responsible for technological advances on procedures and reagents aimed at improving comprehension of genetic changes in solid tumours diagnostic and prognostic applications;

General and specific topics will alternate. In the first instance, in accordance with the scheme of this COST ACTION, two main scientific areas are proposed:
- basic research area: recently disclosed cytogenetic markers of solid tumours: pathogenetic significance; development of region-specific reagents; identification of new cancer genes; updated technological devices.
- translation of new findings on molecular cytogenetics of solid tumours into laboratory services. A few cytogenetic and/or molecular markers of human tumours may be used successfully for inequivocal diagnosis, while other associated markers may have a prognostic meaning. All the chromosomal and molecular markers may serve to monitor remission and relapse of the disease.

D. Timetable and organization

The action is planned for five years. The management committee will meet as soon as the programme starts.

Starting point: First meeting of the management committee.
Definition of the aims: directory, workshops, scientific cooperation, guidelines for diagnostic services.

The coordinator will aggregate all the information provided by the members of the management committee and will assemble the directory of the European labs and scientists involved in basic research and diagnostics concerning molecular cytogenetics of solid tumours. The directory will appear on a web page dedicated to this COST Action and aimed at spreading information on it. The coordinator will be in charge of updating the directory, communicating the workshops which will be organized and the documents/guidelines produced by the COST network.

Based upon an inventory of the activities and interests of the participating groups, the initial meeting of the management group will specify the two areas as described in general terms in the program and will indicate how (what by whom) implementation will take.

WG 1: Working Group for identification of reference labs/experts of specific solid tumours.
WG 2: Working Group on cytogenetics of carcinomas.
WG 3: Working Group on genome resources for FISH analysis.
WG 4: Working Group on advanced molecular cytogenetic technologies.
WG 5: Working Group on genetic predisposition to cancer.
0.5-1 yearPlenary assembly
General meeting of the Working Group in charge of defining reference groups for specific solid tumours ("reference" WG): planning activities of the identified subgroups.
Meeting of the Working Group on cytogenetics of carcinomas.
Joined meeting of the Working Groups on genome resources and advanced molecular technologies bringing together experts from academia and industry.
Communication on the web site of all the proposals and news from the working groups.
First release of the directory.

1.5-2yearsMeeting of the WG on Genetic predisposition to cancer.
Specific solid tumours Working Groups stimulating research efforts in the area related to development of new diagnostic and predictive tools for cancer patient management.
"Rare solid tumours" meeting: set up of European consortia.
Release of updated directory.
Communication on the web site of the agenda of future activities.

2,5-3 yearsPlenary assembly.
Integrated Meeting of the Working Groups on Genome Resources for FISH analysis and Advanced Molecular Cytogenetic technologies: progress report on the application and evaluation of molecular cytogenetic technologies directed to cancer diagnosis, prognosis and prediction of response to particular therapies.
Specific solid tumours workshops: research advances and transfer into diagnostic activity.
Release of updated directory.
Release of recommendations and guidelines for diagnosis of specific solid tumours.

3-4 yearsMeeting of the WG on Genetic Predisposition to Cancer: diagnostic and prognostic use of cytogenetic markers.
Meeting of the WG on cytogenetics of carcinomas: research advances and transfer into diagnostic activity: progress report on new cytogenetic markers.
Specific solid tumours meetings: set up of guidelines to optimize diagnosis.
Release of the updated directory.

4-5 yearsPlenary assembly and meeting of all Working Groups.
Release of guidelines to optimize diagnosis of specific solid tumours and update of existing guidelines.
Plenary assembly and production of a concluding document summarizing the action.

E. Economic dimension

Total cost for the support to this project is estimated at Euros 8 000 000, keeping in mind the number of countries presently involved. However, certain Member States (for example Geece, Spain and Germany) have not been contacted as yet and may be interested; this would increase by 10-20 persons/year the number of participants. The estimated costs will be borne by the different countries involved in the Action.

F. Dissemination

The dissemination will be achieved through the following activities:

- Elaboration and diffusion (web site) of a directory of European laboratories, groups and individual researchers working on the molecular cytogenetic characterization of solid tumours for purposes of basic research or diagnostic activity.

- Set up a list of reference labs for each of the most common solid tumours. Investigators of the identified labs will be in charge of spreading information on recent key findings, relevant publications, diagnostic applications through organization of specific workshops.

- Set up or updating of guidelines for diagnosis of specific tumour types which will be available on the web and published in the international literature together with joined studies within the network upon which they will be based.

- Publication on the web site of annual reports.

ADDITIONAL INFORMATION

- History of the Proposal

The idea of the new COST Action here presented was born in the context of the recently born European Cytogeneticist Association (1997). Fundamental framework of ECA are working groups which aggregate investigators working in a specific field. Interaction among European scientists involved in molecular cytogenetics of solid tumours has stimulated scientific and organization plans that are not likely feasible within the broad association of ECA. Operative focus on the specific sector of solid tumours needs a novel framework that exploits the great resources of expertise and competence represented in a remarkable number of European universities and industrial labs.
The first ECA meeting (Athens, 1997) has played a historical role, as indicated, in coming to the idea of this proposal. The planned action is however fully independent of the organization of ECA.

- Coordinator

Prof. Lidia Larizza
Department of Biology and Genetics for Medical Sciences
Medical Faculty, University of Milan
via Viotti, 3/5
I - 20133 MILANO
Tel:[phone]
Fax:[phone]
E-mail: [e-mail]
Professor of Medical Genetics and Director of Post-Lauream School in Medical Genetics (University of Milan). 1st vicepresident of ECA (European Cytogeneticists Association), in charge of ECA Work Group on Solid Tumours. Former President of Italian Cytogenetics Association (1996-1997), member of the board of SIGU (Societ... Italiana Genetica Umana) 1998, current coordinator of the SIGU Work Group on Oncological Genetics). Fields of interest: Genetic Predisposition to Cancer, Genomics of the Neurofibromatosis 1 region , Molecular cytogenetics of pituitary adenomas.
Author of > 100 publications on peer-reviewed journals, a large majority of which on cancer genetics and cytogenetics.

a) Experts who have been consulted during the drafting of the Proposal

Prof. Felix Mitelman
Department of Clinical Genetics
University Hospital
S-221 85 Lund, SWEDEN
Tel: [phone]
Fax: [phone]
E-mail: [e-mail]
Author of milestone books and reviews on cytogenetics of solid tumours, such as the world-wide known "Catalog of Chromosome Aberrations in Cancer" and "A breakpoints Map of recurrent chromosomal rearrangements in human neoplasia". His lab in Sweden has performed a pionering work on solid tumours, in particular soft tissue sarcomas and is continuously contributing new findings on these and other solid tumours

Prof. Charles Buys
Dept. Med. Genetics - Univ. Groningen
A Deusinglaan, 4
Groningen 9713 AW, NETHERLANDS
Tel: [phone]
Fax: [phone]
E-mail: [e-mail]
Chairman of Dept. of Medical Genetics University of Groningen. He has a special interest in hereditary cancer, in the role of specific chromosome 3 regions in the development of several tumour types and in application to tumour genetics of molecular cytogenetic techniques (interphase and metaphase FISH, fiber FISH, in situ PCR, hybridization of microarrayed genomic DNA).

Prof. Paul Edwards
University Lecturer in Cell Pathology
Department of Pathology
University of Cambridge
Tennis Court Road
Cambridge CB2 1QP, U.K.
Tel: [phone]
Fax: [phone]
E-mail: [e-mail]
Web page http://www.path.cam.ac.uk/~pawe1
He has contributed to detection of breast carcinoma-specific chromosomal rearrangements, which have been precisely mapped by his group applying a wide spectrum of FISH-derived techniques.

Prof. Oscar A. Haas
CCRI, St. Anna Kinderspital
Kinderpitalgasse 6
A-1090 Wien, AUSTRIA
Tel: [phone]
Fax: [phone] or 430
E-mail: [e-mail]
He has been the chairman of the Organization committee of the SECC '99 (Second European Cytogenetics Conference) held in Vienna on July 1999. He has also organized a successfull workshop on Comparative Genome Hybridization (1996), a technique of paramount importance for the study of solid tumours. His group is very active in basic research and diagnosis of pediatric solid tumours.

Prof. Mariano Rocchi
Istituto di Genetica
Via Amendola 165/A
70126 Bari, ITALY
Tel: [phone]
Fax: [phone]
E-mail: [e-mail]
WWW Resources for Molecular Cytogenetics:
http://bioserver.uniba.it/fish/Cytogenetics/welcome.html
He has set up a great resource of FISH probes (Chromosome-specific painting libraries, PCPs (partial painting libraries), YACs (1136) and mouse PACs) which are available to ECA investigators for different aims and researches. Characterization of all the stocked probes makes them an important tool to achieve rapid results in different fields of cytogenetics. Currently tumour cytogenetics resources are being set up as specified on the above Web site.

b) Experts who may be interested in the Action but have, for some reason, not been contacted during the pre-proposal planning

Prof. Manfred Schwab
Dept. Cytogenetics (0825)
German Cancer Research Ctr.
Im Neuenheimer Feld 280
69120 Heidelberg, Baden-Wurttemberg, GERMANY
Tel: [phone]
Fax: [phone]

Prof. Anne Hagemeijer
Center for Human Genetics
Herestraat 49
3000 Leuven, BELGIUM
Tel: [phone]
Fax: [phone]
E-mail: [e-mail]

Programme(s)

• IC-COST - European cooperation in the field of scientific and technical research (COST), 1971-

Topic(s)

• 7 - Medical Research

Call for proposal

Data not available

Funding Scheme

Data not available

Coordinator

N/A

• EU contribution: No data
• Address: Italy
• Total cost: No data