Comprehensive classification for genetic make-up tumours

Information about the genetic make-up of tumours should, in the long term, help clinicians decide on the most effective course of treatment for patients with cancer.

To be most helpful these molecular data must be incorporated into a tumour classification that includes morphological and clinical information.

Jules Berman describes his ideas for a new comprehensive tumour classification in the latest issue of BMC Cancer (http://www.biomedcentral.com/bmccancer).

Berman, the programme director for pathology informatics within the USA National Cancer Institute's cancer diagnosis programme, writes: "This classification is simple (reducing the complexity of information received from the molecular analysis of tumours), comprehensive (providing a place for every tumour of man), and consistent with recent attempts to characterise tumours by cytogenetic and molecular features.“

"Traditionally, tumours have been classified by their morphologic appearances,“ he continues. "Unfortunately, tumours with similar histologic features often follow different clinical courses or respond differently to chemotherapy.“

Current tumour classifications suffer from a number of problems. Firstly, they are created piecemeal for specific sites or organ systems. Nobody has published a comprehensive classification, although comprehensive taxonomies have been attempted. Secondly, they are often based on medical disciplines, rather than on any biologic principles. Thirdly, a given tumour will appear redundantly when subclassifications are merged. Finally, no tumour classification has been prepared in a standard format designed to exchange, merge or analyse heterogenous biological data.

The alternative, a classification based solely on the molecular characteristics of tumours, would sacrifice the clinical/pathological experiences that inform virtually every clinical decision related to the diagnosis and treatment of patients with cancer.

Both the type of cells from which a tumour is derived and the molecular characteristics of those cells determine how a tumour will behave ­ information of great importance to clinicians. Berman has organised his classification using these two features.

At the highest level of the classification, tumours are grouped according to the component cells' developmental history ­ their ahistogenesis'.

For example leukaemia would be classified as a mesenchyme-derived tumour. Patterns identified from the gene expression and proteomic data from tumour samples can then be integrated as new groups within this classification.

Berman writes: "Some of these groupings will prove to have a specific biologic feature, for example an increased tendency to metastasise, a higher response to a chemotherapeutic agent or lengthened survival.“

As each tumour is derived from a cell with an individual lineage, it will have a unique position within the classification. The commonly used tumour classifications list tumours by the body site of origin.

However, every organ contains connective tissue, vessels, and lymphoid tissue. When you start to list the tumours that can occur in an organ, you find that every organ can develop many of the same tumours. Classifications that are organised by anatomic site become massively redundant, and this becomes a major problem when dealing with many thousands of tumour terms that link to other biologic datasets.

"A good classification system should help drive down the complexity of enormous databases and help us discover relationships among different data elements by assembling data under sensible group hierarchies,“ writes Berman. "The most important value of this (new) classification is the disengagement of tumour type and tumour place of originaThis permits tumours with similar molecular profiles to be classified according to biological attributes rather than anatomical location.“

The classification outline (in XML) and the latest version of the classification (with 55 000 entries) are available with the article as supplemental open access documents that can be used or criticised freely by the biomedical community.

Features of the tumour classification

There is a 12-point list of features associated with Berman's system of tumour classification:

1. Each tumour occurs only once in the classification.

2. The classification is comprehensive (every tumour of man can be placed in the classification.

3. The classification is simple. One of the purposes of a classification is to drive-down the complexity that exists when the domain taxonomy is large. The entire classification is described by under 40 classifiers.

4. Other tumour classifications divide tumours by medical specialty (such as dermatologic neoplasms, hematologic neoplasms and thoracic neoplasms). This classification is based on biologic principles. The classification uses a feature from developmental biology to capture the most important genomic dichotomy in tumour biology, the separation of tumours with simple and characteristic genetic abnormalities from tumours with genetic instability.

5. The classification has acompetence'. In the field of informatics, competence is the ability to answer questions related to the instances of a data group.

6. The classification is represented as an XML document.

7. It is easy to add subdivisions to the classification. This is important, as the molecular analysis of tumours is likely to provide new taxa.

8. It is easy to move subdivisions of the classification. Classifications are hypothetical recreations of reality and must be changed as information is accrued.

9. The classification is easily understood by developmental biologists. Developmental biologists are major participants in post-genomic science and need to have tools to relate basic research with clinical exigencies.

10. The classification is compatible with modern theories of the astem cell' origin of tumours.

11. The classification does not invalidate existing diagnoses found in pathology reports. The medicolegal importance of this feature cannot be exaggerated. This relieves pathologists from reviewing all their prior cases and re-diagnosing them in conformance with a new classification.

12. The classification is an open access document that can be used or criticised freely by the biomedical community.

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