Project title

 

'Atlas of Genetics and Cytogenetics in Oncology and Haematology'

internet journal / encyclopaedia /database http://AtlasGeneticsOncology.org

 

 

Summary

 

The Atlas is a peer reviewed internet journal / encyclopaedia / database devoted to:

- genes implicated in cancer,

- cytogenetic or clinical entities in cancer, and

- hereditary diseases which are cancer-prone conditions.

Size of the Atlas in 2015: number of pages: 45,500; 3,500 authors; 5,500 visits every open day; 1,1 million unique user every year (USA 27%).

 

 

Key words

 

- Pooling of knowledge concerning the biology of normal and cancerous cells,

- Referential and investigation tool for research,

- Multilingual pedagogical support,

- Translational health research

- Transfer of scientific innovation towards research itself, and, downstream, towards patient care

 


Context

 

25,000 new publications concerning cancer genetics in man are added each year in PubMed. No one, anymore, has the whole required knowledge, necessary to guide the treatment procedure in case of a rare disease. Huge database are therefore needed, to collect and summarize data on these rare diseases, and produce meta-analyses.

 


Objectifves of the project


- Medical treatment assistance in rare forms of cancer,

- Efficiency savings in the fight against cancer,

- Decrease in fundamental and applied research as well as medical costs.

- Personalised medicine for cancer (one of the axes of the cancer plans).



I- Scientific Background

General description / relevance and originality of the project Prognosis of a leukaemia depends on the genes involved: 5 years survival: 6% in the inv(3)(q21q26) RPN1/MECOM leukemia, 100% in the  dic(9;12)(p13;p13) PAX5/ETV6 leukemia. And treatments, indeed, depend on the severity of the disease. However, 2,000 to 9,000 genes are possibly implicated in cancer, and 1,200 types of solid tumours exist. Some cancers are frequent while many others are very rare (only 1 published case), this is particularly true for leukemias subtypes … but there are more than 900 leukemias!No one, anymore, has the whole required knowledge, necessary to guide the treatment procedure in case of a rare disease. Huge database are therefore needed, to collect and summarize data on these rare diseases, and produce meta-analyses. L’ Atlas contributes to 'meta-medicine', this mediation between the knowledge and the knowledge users in medicine.

II- International positioning of our team / Current organization

The Atlas is one of the pioneers of the Internet, it started in 1997. It meant writing short cards on genes and chromosomes implicated in cancer. The Atlas is now 45,500 pages big, written by more than 3,500 authors, from about 50 countries (France, USA, Italy, United Kingdom, Germany, Japan, Spain, Canada, China, The Netherlands ...).

The Atlas is in free access, which is particularly useful for third world countries or for students.

- Topic research The Atlas participates in research on cancer epidemiology. The Atlas is a tool in genomic studies of the latest generation (see Science 28 Jan 2011, vol 331 p 435-439, suppl data, where the authors indicate that they have used the Atlas and Cosmic as reference databases to choose and test a series of genes in medulloblastoma in childhood). Nonetheless, the Atlas' aim is not to overlap with the databases daily used in molecular biology (UCSC, Ensembl, Entrez, Cosmic, Swiss-Prot). However, as these data are in the public domain, we could easily produce them, according to the needs of the community.

- Topic teaching and continuing medical education The Atlas is at the crossroads of research, university and post-university teaching (virtual medical university) and telemedicine. 

- Database on genes: Where else can be found so many detailed articles on genes? see: PTN or BCL6 http://atlasgeneticsoncology.org//Genes/PTNID41904ch7q33.html and http://atlasgeneticsoncology.org/Genes/BCL6ID20.html.

- Electronic journal version of the Atlas An Open access electronic journal /pdf version of the Atlas is being developed by Institute for Scientific and Technical Information (INIST) of the French National Centre for Scientific Research (CNRS). Available are the archives of a quarterly journal since 1997, which became a bimonthly journal in 2008 and a monthly journal in 2009, comprising 2,500 articles in more than 120 volumes, which constitutes a 10,000 pages collection, available at: http://irevues.inist.fr/atlasgeneticsoncology, allowing the Atlas, soon, to be referenced by the main bio-medical databases, including PubMed.

- The Atlas combines various types of knowledge all on one site: Genes and their function, cell biology, diseases, cytogenetics, but also clinical genetics, including hereditary diseases which are cancer-prone conditions. This tends to unify cancer genetics, while data are elsewhere dispersed between several sites[1]. The iconography in the Atlas is diverse (medical imaging, pathology, chromosomes, 3-D structure of proteins, genetic maps...), which is not found in other sites (apart from genetic maps that can be found in GeneBank, Ensembl …). The Atlas is the only site devoted to genetics where the prognosis is quoted:  It has always seemed surprising to us that such a crucial data is just ignored in other sites. There are more than 17,000 internal hyperlinks in the Atlas.

- Diagnosis assistance and information-based therapeutic decision The Atlas contributes to the cytogenetic diagnosis and may guide treatment decision making, particularly regarding rare diseases (because they are numerous, rare diseases are frequently encountered).

- Developments in cell biology and physio-pathology: data in the Atlas are a definite resource in cell biology and physio-pathology, that we are just beginning to harness (e.g.: Apoptosis: http://atlasgeneticsoncology.org/Categories/Apoptosis.html ).

- Towards a personalized medicine of  cancer: From our section "Genes", can be extracted 322 genes implicated in colorectal cancer, 457 in breast cancer, and 589 genes in prostate cancer (see paragraph "Other genes implicated " at: http://atlasgeneticsoncology.org//Tumors/breastID5018.html ). With the fast development of technics in genetics, it now emerges that many subtypes of solid tumors may exist, following the leukemia model (how many hundreds of breast cancer subtypes, defined by distinct genetic profiles, to be uncovered?). Recently, new data on lung adenocarcinoma made possible to consider personalized medicine (see http://atlasgeneticsoncology.org/Tumors/TranslocLungAdenocarcID6751.html ). This, together with cell biology developments in the Atlas demonstrates that the encyclopedic content is potentially a basis for developing personalized medicine for cancer. It remains to present this knowledge in such an affordable manner that the Atlas truly becomes a tool for the staff meetings. 

Renown Prestigious journals, such as Science and Nature Reviews Cancer, have written about the Atlas The Atlas is regularly cited as a journal in leading scientific publications (Annual Review of Biochemistry (Impact Factor 29,88), Science (29,75), Nature Reviews Cancer (29,54), Cancer Cell (25,29), Nature Cell Biology (19,53), Journal of the National Cancer Institute (14,07), American Journal of Human Genetics (12,30), Molecular Systems Biology (12,13), Genes and Development (12,08), Genome Research (11,34), Trends in Molecular Medicine (11,05), Blood (10,56), PNAS (9,43)...). The Atlas is also cited as a reference database in Science. Hyperlinks towards the Atlas have been developed by the National Cancer Institute USA, Swiss-Prot, GeneCards, the Sanger Institute, Mitelman database au NCI, etc... Renown of the Atlas may be checked at: http://chromosomesincancer.org/en/jce/acknoledgements-to-the-atlas.html (Felix Mitelman wrote that the Atlas "has grown into a truly monumental encyclopaedic work of great importance to cancer research (...) an invaluable reference and resource for scientists and clinicians").

Who uses the Atlas?The Atlas is accessed by: 1- Research: cytogenetics, molecular biology, cell biology researchers; 2- Hospital: clinicians, haematologists, cytogeneticists, pathologists, from the teaching hospitals, indeed, but also from general hospitals where the Atlas is one of the rare free resources. Junior doctors in haematology or oncology, are also most receptive to the Atlas that they see as a training and educational tool; 3-Students.

The Atlas receives more than 1,100,000 visits every year (25% of the visitors are from the USA, 12% from France, but many other visitors are from the developing countries. 200 cytogenetic labs come every day, 1,000 visitors more than once a week (cytogenetic labs./university teachers-researchers), and 6,000 visitors more than once a month (university teachers - researchers, students, staff meetings on blood malignancies). 5,500 individual machines connect to us every day. A bug, on May the 23rd, 2008, was devastating: pages on chromosomes, with their data, had vanished; many mails were sent to us, proving that the Atlas was (is) indispensable; see: http://chromosomesincancer.org/en/jce/acknoledgements-to-the-atlas.html#Incident ). See also recent testimonies at :http://atlasgeneticsoncology.org/Supporting_Atlas_First_signatories.pdf

The Atlas is also operated by various biotech and pharma to implement their internal systems and databases.

Comparison with the Mitelman Databasethe Atlas is certainly not redundant with the "Mitelman". As a matter of fact, the Mitelman and the Atlas are complementary: the Mitelman is exhaustive but gives rough data, with no annotation, while the Atlas presents a meta-analysis of the data, giving an overview on a given disease, describing the main clinical characteristics, with, when possible, an iconography of chromosomes (e.g. see: t(1;11)(p32;q23) in each of the two sites).

Scientific societies have decided to grant the Atlas, they thus give a scientific credibility and a clear and real will to the Atlas sustainability and perennialty: Association des Cytogénéticiens de Langue Française et Groupe Francophone de Cytogénétique Hématologique, Belgian Society of Human Genetics et Belgian Cytogenetics Group in Haematology and Oncology, Dutch working group of Tumor Cytogenetics, Berufsverband Deutscher Humangenetiker e.V. et Gesellschaft für Humangenetik e.V., Societa Italiana di Genetica Umana, Grupo Cooperativo Español de Citogenética hematológica and Sociedad Española de Hematología y Hemoterapia, Australasian Society of Cytogenetics. 

Structure of the board of the Atlas

- Jean-Loup Huret, associate professor and consultant, CHU Poitiers, editor in chief and Philippe Dessen, research director, CNRS-Institut Gustave Roussy, database director;

- Because, historically, the project could not have been supported by institutional players, a non-profit association (french law 1901) was created (see http://chromosomesincancer.org/en/ ) (president Jean-Loup Huret, geneticist, vice president Hossein Mossafa, geneticist, treasurer Bernard Drochon, external auditor, secretary Martine Jammet, entrepreneur, all volunteers). This association have employed 5 to 6 MSc or PhD co-workers (the main area of expenditure: 30,000 Euro (salary + charges) for each collaborator, but they make an indispensable work -since the Atlas is much more an encyclopedia than a database, requesting a good amount of expertise). The association comprises about 60 members (50% french, 25% americans).

- A scientific committee of the association (http://chromosomesincancer.org/fr/jce/conseil-scientifique.html ), including delegates from various scientific societies; and there is also an editorial board for the Atlas (http://atlasgeneticsoncology.org/Backpage.html#EDITORIAL ).

III- Development steps

To reach its principal object -the patient service-, the Atlas must become "clinic orientated". To encourage the clinical physician to use the Atlas in his decision making, the Atlas must provide the required information, and such in a "clinician friendly" manner.

A part of our activity must be dedicated to bioinformatics developments, at a time when new fields of cytogenetic are developing with the massive use of FISH, CGH, exome and genome sequencing. Numerous and precise data on mutations, structures variations as well as on gene fusions are taking over the literature.

Adding information with a clinical orientation and into a customized therapeutic care. Developing the knowledge and the scientific innovation transfer into the care system, in particular as part of targeted therapies. Developing decision trees (using the High Authorities recommendations for each pathology); making a list of all the examinations to be performed according to each step of the