CIT Program Tumor Identity Cards: Difference between revisions

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{{refimprove|date=January 2022}}{{short description|Tumors research program}}

{{Multiple issues|orphan = April 2012|refimprove = December 2013|

The '''"Cartes d'Identité des Tumeurs (CIT)" program''',<ref>{{Cite web |date=2021-06-03 |title=Le programme « Cartes d'Identité des Tumeurs » {{!}} Ligue contre le cancer |url=https://www.ligue-cancer.net/articles/le-programme-cartes-didentite-des-tumeurs |access-date=2024-06-13 |website=www.ligue-cancer.net |language=fr}}</ref> launched and funded by the French charity "[https://www.ligue-cancer.net/ Ligue Nationale contre le Cancer]," aims to improve or develop better targeted therapeutic approaches by refining molecular knowledge of multiple types of tumors. The CIT program mainly relies on the [[Omics|large-scale and systematic profiling]] of large cohorts of tumors at various molecular levels including at least the [[genome]], the [[epigenome]], and the [[transcriptome]].

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== See also ==

[[Image:CIT-Tumor-Samples-20100507.png|thumb|upright=2.5|The CIT Program database contains more than 10,000 cancer samples]]

* [[Precision medicine]]

* [[Oncology]]

The '''"Cartes d'Identité des Tumeurs (CIT)" program''' (or 'Tumor Identity Cards'), launched and financed by the [[France|French]] [[Charity organization|charity]] "Ligue Nationale contre le Cancer", aims at characterizing multiple types of [[tumors]] through the coupled genomic '''analysis of gene expression and chromosomal alterations'''.<ref>{{cite web|title=Official Web Site|url=http://cit.ligue-cancer.net/|accessdate=3 September 2013}}</ref>

* [[Cancer Research]]

* [[Bioinformatics]]

== Towards personalized treatments ==

* [[Computational genomics]]

* [[Oncogenomics]]

The "Cartes d'Identité des Tumeurs (CIT)" program should benefit each patient by contributing to :

* [[Genomics]]

* [[Transcriptome]]

* more accurate [[Medical diagnosis|diagnosis]]

* [[Gene expression profiling]]

* better predictions of the response to [[Therapy|treatment]] and the disease progression

== References ==

* improved patient follow-up during and after treatment

{{Reflist}}

== Collaborations throughout the whole of France ==

Built with a network of researchers, [[pathology|pathologists]], doctors and [[bioinformatician|bioinformaticians]], the "Cartes d'Identité des Tumeurs (CIT)" program involves 60 teams and offers one of the largest tumor [[databases]] in Europe containing more than 8,000 annotated tumor [[samples]] and 10,000 micro-array experiments.

== A set of standardized processes and technologies ==

=== Curation and standardization of biological and clinical annotations ===

All the information on the patients is de-identified and sent on by the clinical centers. All the clinical follow-up data, including the results of the various biological and [[Genetic testing|genetic tests]] carried out on the patients, are included in a database with secure access (Annotator).

This CIT program database also contains data generated by each of the technological platforms and the results of the analyses. At each stage of the [[data integration]] process, all the information is checked to ensure that it is complete and consistent. The annotations are then recoded in accordance with internal and [[international standards]]. This allows for cross-project analyses.

=== DNA/RNA Extraction and Qualification ===

The quality of the biological resources constitutes a major element in the [[reproducibility]] of the results obtained in the [[Genomics|genomic]] studies.

To this end, the CIT program has set up a platform dedicated to the extraction and qualification of [[RNA]] and [[DNA]]. The extraction of RNA and DNA is carried out from the same tumor sample. The quality of the samples is assessed using [[Agarose gel electrophoresis|agarose gels]] and electrophoregram profiles in order to evaluate the level of contamination and [[biodegradation|degradation]] of these biological resources.

All the samples are processed on the same platform, with validated and standardized protocols, to optimize the yield of the platform, to implement precise [[quality control|quality controls]], and to improve the performance of the subsequent [[hybridization|hybridizations]] even in case of partial degradation of the tumor samples. Depending on the quality of the surgical procedure, the volume of available [[biomaterial]] and the type of pathology, between 0 and 60% (average 25%) of the sample RNAs are filtered out by the platform.

=== Biochip Experiments ===

The CIT program chooses commercial technologies and efficient instruments to carry out the hybridizations on biochips (especilly [http://www.affymetrix.com/estore/browse/products.jsp?productId=131455&categoryId=35760&productName=GeneChip-Human-Genome-U133-Plus-2.0-Array#1_1 Affymetrix GeneChip arrays] to study the expression of genes, [http://www.illumina.com/technology/beadarray_technology.ilmn Illumina BeadArrays] to study allelotypes, SNPs and [http://www.illumina.com/applications/epigenetics/array-based_methylation_analysis.ilmn methylome], and next-generation sequencing of [[exome|exomes]] and [http://www.illumina.com/applications/epigenetics/small_rna_analysis.ilmn miRNAs]). This increases the yield of the platforms and the reproducibility of the results. Standardized protocols are set up at all stages of the process (preparation of the samples, hybridization, scanning, image analysis etc.). A key objective of the CIT program is to process the greatest possible number of samples on the same platform to minimize [[bias]] related to the experiments, to optimize the parameters of the different stages, and to enable comprehensive quality control checks.

Between January 2004 and January 2013, over '''14,000 [[biochip]] experiments''' were carried out.

=== Analysis & Validation ===

CIT Biostatistical expertise

The data processing procedures are based on reference methods from the literature or on [http://cit.ligue-cancer.net/?page_id=63 innovative internal developments]. Implemented with the [[Open-source software|open source]] [[R (programming language)|statistical software R]], they follow a set of specifications which facilitate collaborative work and tracking.

==== Pre-processing ====

The data sent by the hybridization platforms are pre-processed according to a normalization and quality control stage adapted to each technology: background correction, quality control, filtering, aggregation and normalization. For genomic data ([[Comparative genomic hybridization|CGH]], [[SNPs]]), an essential segmentation step is added to identify the altered regions along the genome.

==== Data analysis ====

The data analysis unfolds into three main stages:

* Class discovery, using unsupervised [[clustering]], enables the identification of the underlying [[molecular]] groups. The quality and variety of the supplied annotations are crucial to interpret the resulting classification.

* Class comparison, through a supervised approach, defines a molecular signature, i.e. the set of markers associated with a given [[phenotype]].

* Class prediction, using classification approaches, establishes the smallest combinations of molecular markers to characterize tumor groups and to guide decisions about medical treatments.

==== Interpretation and Validation ====

Results are interpreted through additional bioinformatics analysis (pathway analysis, combined genome and [[transcriptome]] study), and then validated against independent datasets from the literature or from the CIT program. Finally, a validation of the results is carried out with [[RT-PCR]] on a [[Microfluidics|microfluidic]] platform.

== References ==

<references />

== External links ==

* [http://cit.ligue-cancer.net/?page_id=804&lang=en Official web site (in French)]

* [https://web.archive.org/web/20160513061454/http://cit.ligue-cancer.net/?page_id=791&lang=en List of main scientific publications]

* [http://cit.ligue-cancer.net/pdf/AnnotatorCurationProcess.pdf Annotations Curation and Standardization (2009)], from the CIT Program web site

* [http://cit.ligue-cancer.net/pdf/AnnotatorCompletionRate.pdf Clinico-biological Annotations in the Annotator® database (2009)], from the CIT Program web site

* [http://cit.ligue-cancer.net/pdf/QualityControlPlatform.pdf DNA/RNA Extraction & Qualification (2009)], from the CIT Program web site

* [http://cit.ligue-cancer.net/pdf/BiostatAnalysis.pdf Data Analysis & Validation (2009)], from the CIT Program web site

* [[:fr:Programme Cartes d'identité des tumeurs|French version of this page]]

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[[Category:Biostatistics]]

[[Category:Cancer research]]