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This week’s article was inspired by a question from a reader in Sacramento, California: Mary Pat Hartman, RN
“Thank you for your informative articles on cancer. I am an RN in pediatric intensive care and have had some infant patients that were born with cancer such as Leukemia and Ewing’s Sarcoma. How is it possible to have cancer before you are born?”
While I have written about the relationship between age and cancer, I would like to preface this article by emphasizing how rare childhood cancers are: from 2003-2007, an average of 1.8 per 10,000 kids under one year of age will die from cancer. That statistic stands as a stark contrast to the 80-84 year age bracket: 1,423 per 10,000.
To biologists, the process from conception to birth is known as development. During development, a single cell gives rise to trillions, representing hundreds of different cell types and diverse tissue architectures developed from the aforementioned process. It’s an immensely complex process of cell division and differentiation: differentiation is the process by which one cell type becomes two. In the process of differentiation, a progenitor cell will divide and give rise to another progenitor cell, along with a more specialized descendant. Depending on the context, these progenitor cells are called stem cells. Each time a cell divides, numerous genetic changes (mutations) can occur, and the rate of division during development is tremendously high. Also, each time tissues differentiate, it is possible to have some cells not complete differentiation.
(The above graphic illustrates a variety of cell and tissue types that can arise from progenitor stem cells during development. In reality, there are many intermediate cell types that bridge the gap between stem cells and mature tissues, represented by the arrows. Various childhood cancers can be thought of as stuck along that route. Image: SigmaAldrich)
Tumor cells are often less differentiated than their normal counterparts, and are more ambiguous in their identity and more adaptable to different environments. Progenitor (non-mature) cells are more resistant to apoptosis, and are often more capable of migrating through tissues, which are two of the hallmarks of cancer. In adult cancer models, cancers either arise from normal cells that de-differentiate, or from small populations of adult stem cells. Pediatric cancers often arise from progenitor cells in development that never differentiate completely: they are sort of like the grade school brats that never grow up.
Acute Lymphoblastic Leukemia (ALL) is one of the most common childhood blood cancers, although it can also present later in life as well. ALL is essentially a condition where non-mature (brat) white blood cells accumulate in massive numbers in the blood, unable to “grow up” into white blood cells.
Ewing’s Sarcoma and Neuroblastoma (two of the most common non-blood cancers in children) arise from neural crest cells (a type of progenitor stem cell late in development) that are especially prone to migration and are able to survive in many different tissue niches. As I alluded to before, they naturally have several similarities to tumor cells!
In light of this, it is amazing to many that children are not born with cancer more frequently!
A curious example of differentiation in cancer therapy (or lack thereof) is with a special type of Neuroblastoma: Stage 4S. When diagnosed, the doctors do nothing. They often send the kid home. Most of the time, these tumors will spontaneously differentiate into benign tissues and become cancer no more. Oncologists also commonly use differentiation agents, like retinoic acid, to cause other grades of neuroblastomas to do the same (1). This therapy is often used by our oncologist collaborators at Rady Children’s Hospital in San Diego (2).
In summary, childhood cancers have much in common with adult cancers in their ability to spread, divide quickly, and disrupt tissues. But, while adult cancers can usually be thought of as a result of years and years of cumulative damage, childhood cancers can be thought of more like developmental defects, similar in cause to a cleft lip.
Thank you for reading!
1) Armstrong, JL, Redfern, CP, Veal, GJ. 13-cis retinoic acid and isomerisation in paediatric oncology–is changing shape the key to success? Biochem Pharmacol 2005;69(9):1299-306.
2) Personal communication, Dr. Jennifer Willert.
Key Words: Pediatric Cancer, Prenatal Cancer, Ewing’s Sarcoma