Tumor Speciation
Neoplasms: Principles of Development and Diversity
Jules J. Berman, Ph.D., M.D.
TUMOR SPECIATION
On February 12, the world celebrated the 200th anniversary of Charles Darwin's birth. Darwin is best known for explaining speciation; how life on earth diversifies into distinct types of organisms. Each species shares a characteristic set of traits that separate the species from all other species on earth. One of the most curious aspects of speciation is member uniqueness: every species is composed of members that are different from every other member of the same species. If each species is composed of genetically diverse members, how can we think in terms of "sameness" among the members of a species?
Speciation is a general phenomenon, not confined to animals. For example, the field of cancer research deals with many different kinds (species) of tumors. The phenomenon of tumor speciation is basically the same as the problem of animal speciation. tumors, like animals, occur as highly distinctive types, but every tumor is genetically unique, different from every other tumor that has ever occurred or that will ever occur.
Although there are many kinds of tumors that can arise in humans and other animals, pathologists (the people who render diagnoses on tissue specimens) are adept at assigning names to every tumor occurrenc: Warthin's tumor of salivary gland, fibrolamellar carcinoma of liver, papillary carcinoma of thyroid, carcinoid tumor of appendix, and many others. Each kind of tumor has a characteristic appearance when it is viewed under a microscope. Pathologists can instantly render a specific diagnosis on most human tumors. Genetic analyses of cancers conducted over the past decade have shown us that cancer is a complex disease, with tumors accumulating thousands of different genetic alterations as they grow. This being the case, why do we encounter distinctive tumor species? Should we not expect a free-for-all of infinitely diverse, unique tumors? In addition, we now know that tumors continue to collect genetic changes over time. Should we not expect tumors to change their type over time, one day seeming to be a carcinoma (tumor of epithelium), and another day seeming to be a lymphoma (tumor of the immune system) or a sarcoma (tumor of the connective tissues)?
In fact, this never occurs. Just as a cat never becomes a dog, and a hamster never becomes a frog; a lymphoma (a tumor of lymph cells) never becomes an adenocarcinoma (a tumor of glandular epithelial cells), and a melanoma (a tumor of melanin producing cells of the skin) never becomes a glioma (a tumor of the central nervous system cells).
How do we reconcile the uniqueness of every tumor with the constraints of tumor speciation?
This problem is fundamentally the same problem as animal speciation. In the case of animals, speciation occurs because of the genetic diversity among the different members of a species. New species arise from mating among a subpopulation of a species that preserves genetic traits that are expressed within the subpopulation, and that are not expressed in the general population of the species. If the individual animals within a population were genetically identical, and could not express new traits in subpopulations, speciation, would not occur. When a new species appears, it has properties of the parent species, but it also has traits that distinguish it from the parent species and every other species on earth.
In cancers, speciation is also a genetic phenomenon occurring in cellular subpopulations. During carcinogenesis (the process of cancer development), new genetic traits are acquired by developing tumor cells. The story of what these new traits are, and how they are acquired, has captured the attention of a generation of molecular biologists. Without going into the minutiae of cancer genetics, it suffices to say that cancer cells acquire many mutations. Some of these cancer mutations code for proteins that enhance cellular activities associated with malignant behavior, such as increased growth rate and motility. Other cancer mutations are associated with cellular activities that decrease or inhibit normal cellular functions: DNA repair and gene maintenance, controlled cell death, and sensitivity to growth inhibitors. We know that the genetic alterations associated with cancer always have a narrow cell specificity. An acquired genetic alteration may appear consistently in only one type of cancer, and an inherited cancer-causing mutation, that occurs in every cell of the body, may result in tumors of only a specific cell type.
The human body has several hundred different kinds of cells, and these cells pass through many different developmental stages on their way to becoming the fully functional cells we find in adult bodies. Each type of cell is defined by the metabolic pathways it expresses. Mutations in a cell can only be expressed when the cell expresses the gene mutation within a metabolic activity. Every neoplasm, despite its genetic uniqueness, has a set of properties determined by the metabolic pathways available to its cell of origin. This set of properties, including microscopic appearance, will be shared by other tumors arising from the same cell. Each of the many different species of tumors occurring in humans and animals has a microscopic appearance and biological behavior that has traits of the type of cell from which it arose. In addition, each type of cancer has a set of neoplastic traits whose expression is constrained by the pre-existing cellular pathways inherited from the parent cell type.
This explains how it is possible that every tumor that has ever occurred is a unique biological entity; and yet, every tumor that has ever occurred can be classified as a distinctive species that shares morphologic and biological features with every other tumor of the same kind.
I have heard it said that Charles Darwin's "On the Origin of Species," has negligible impact on our daily lives. This is not so. Aside from its enormous impact on every aspect of the natural sciences, it is the basis for much of modern medicine: genetics, molecular biology, and pharmacology. Just as our knowledge of animal speciation permits us to organize and make sense of life on this planet, our knowledge of tumor speciation permits us to organize tumors into classes that share common sets of metabolic pathways that account for their malignant properties: persistent growth, invasion, and metastasis. Drugs that control these pathways in any given tumor, will likely control the same pathways in all tumors of a common class. When we know the class of a species of tumor, we have a way of developing cures that apply to every species in the class.
- © 2009 Jules J. Berman
Tumor speciation is just one of many topics covered in my book, Neoplasms, Principles of Development and Diversity. Additional information is available at the publisher's web site.
key words: neoplasm, classification, cancer, tumour
Web site created Feb. 19, 2009
