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Fossilized evidence of a tumor in a 255-million-year-old mammal forerunner

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Credit: Christian Sidor/Megan Whitney

When paleontologists at the University of Washington cut into the fossilized jaw of a distant mammal relative, they got more than they bargained for — more teeth, to be specific.

As they report in a letter published Dec. 8 in the Journal of the American Medical Association Oncology, the team discovered evidence that the extinct species harbored a benign tumor made up of miniature, tooth-like structures. Known as a compound odontoma, this type of tumor is common to mammals today. But this animal lived 255 million years ago, before mammals even existed.

"We think this is by far the oldest known instance of a compound odontoma," said senior author Christian Sidor, a UW professor of biology and curator of vertebrate paleontology at the Burke Museum of Natural History and Culture. "It would indicate that this is an ancient type of tumor."

Before this discovery, the earliest known evidence of odontomas came from Ice Age-era fossils.

"Until now, the earliest known occurrence of this tumor was about one million years ago, in fossil mammals," said Judy Skog, program director in the National Science Foundation's Division of Earth Sciences, which funded the research. "These researchers have found an example in the ancestors of mammals that lived 255 million years ago. The discovery suggests that the suspected cause of an odontoma isn't tied solely to traits in modern species, as had been thought."

In humans and other mammals, a compound odontoma is a mass of small "toothlets" amalgamated together along with tooth tissues like dentin and enamel. They grow within the gums or other soft tissues of the jaw and can cause pain and swelling, as well as disrupt the position of teeth and other tissues. Since odontomas do not metastasize and spread throughout the body, they are considered benign tumors. But given the disruptions they cause, surgeons often opt to remove them.

Surgery was not an option for the creature studied by Sidor's team. It was a gorgonopsian, a distant mammal relative and the apex predator during its pre-dinosaur era about 255 million years ago. Gorgonopsians are part of a larger group of animals called synapsids, which includes modern mammals as its only living member. Synapsids are sometimes called "mammal-like reptiles" because extinct synapsids possess some, but not all, of the features of mammals. The first mammals evolved over 100 million years ago.

"Most synapsids are extinct, and we — that is, mammals — are their only living descendants," said Megan Whitney, lead author and UW biology graduate student. "To understand when and how our mammalian features evolved, we have to study fossils of synapsids like the gorgonopsians."

Paleontologists have categorized many "mammal-like" features of gorgonopsians. For example, like us, they have teeth differentiated for specialized purposes. But Whitney started studying gorgonopsian teeth to see if they had another mammalian feature.

"Most reptiles alive today fuse their teeth directly to the jawbone," said Whitney. "But mammals do not: We use tough, but flexible, string-like tissues to hold teeth in their sockets. And I wanted to know if the same was true for gorgonopsians."

A purely external examination of gorgonopsian fossils wouldn't answer this question. Whitney had to take the risky and controversial approach of slicing into a fossilized gorgonopsian jaw: looking at thin sections of jaw and tooth under a microscope to see how the tooth was nestled within its socket. Since this technique would damage the fossil, Whitney and Larry Mose, a UW undergraduate student working with her, used a solitary or "orphan" gorgonopsian lower jaw that Sidor had collected in southern Tanzania.

Mose prepared multiple thin slices from the gorgonopsian jaw — each only about as thick as a sheet of notebook paper — and mounted them onto slides. He and Whitney immediately noticed something unexpected within the jaw: embedded next to the root of the canine were irregular clusters of up to eight tiny, round objects.

At higher magnification under a microscope, Whitney discovered that the objects within each cluster resembled small, poorly differentiated teeth, or toothlets. The toothlets even harbored distinct layers of dentin and enamel.

"At first we didn't know what to make of it," said Whitney. "But after some investigation we realized this gorgonopsian had what looks like a textbook compound odontoma."

At 255 million years, this is by far the oldest reported evidence for an odontoma — and possibly the first case in a non-mammal. According to Sidor, odontomas have been reported in archaeological specimens, as well as fossilized mammoths and deer. But those cases all date to within the last million years or so. Since this synapsid had an odontoma, it would indicate that this mammalian condition existed well before the first mammals had evolved.

"This discovery demonstrates how the fossil record can tell us a lot about our present-day lives — even the diseases or pathologies that are part of our mammalian heritage," said Sidor. "And you could never tell that this creature had it from the outside."

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The research was funded by the National Science Foundation and a University of Washington Mary Gates Research Fellowship.

For more information, contact Sidor at [email protected] and Whitney at [email protected] Sidor and Whitney have also prepared answers to a list of frequently asked questions, which can be found below, regarding gorgonopsians, tooth development, odontomas and more.

Grant number: NSF EAR-1337569.

Frequently asked questions: odontoma in a gorgonopsian

Prepared by Christian Sidor and Megan Whitney with the University of Washington and the Burke Museum of Natural History & Culture.

Major findings

Our discovery of odontoma in a gorgonopsian fossil demonstrates that this type of tumor has existed for at least 255 million years and predates mammals.

Frequently Asked Questions

What are gorgonopsians?

  • Gorgonopsians were a group of carnivorous, land-based vertebrates that lived between about 270 to 252 million years ago during the middle and late Permian Period. Their fossils are known from Africa and Russia.
  • Gorgonopsians are distantly related to living mammals, but they lie "on the mammalian line," meaning that they are more closely related to humans than to dinosaurs or other reptiles.
  • Gorgonopsians ranged in body size from 2 to 10 feet long, from the length of a bobcat to that of a polar bear.
  • Gorgonopsians are sometimes known as the "saber-tooths of the Permian," for their enlarged canine teeth.

What is an odontoma?

  • The World Health Organization defines a compound odontoma as: "A malformation in which all the dental tissues are represented in a more orderly pattern than in the complex odontoma, so that the lesion consists of many tooth-like structures. Most of these structures do not morphologically resemble the teeth of the normal dentition, but in each one enamel, dentine, cementum and pulp are arranged as in the normal tooth."
  • Odontomas are one of the most common odontogenic tumors, constituting approximately 20 percent of odontogenic tumors. Ameloblastoma is the most common with 39.6 percent of odontogenic tumors.
  • Odontomas are not cancer. They are considered benign tumors, though in humans they are often surgically removed.

Where was this specimen found?

  • The gorgonopsian jaw with the odontoma was found in southern Tanzania in the Ruhuhu Valley in 2007.
  • The specimen is about 255 million years old, based on dating of similar fossils in South Africa.

How did we find this pathology?

  • There were no external indications of a pathology. We were thin-sectioning this specimen for an entirely different project — examining the tissues involved in tooth attachment.
  • UW undergraduate researcher Larry Mose noticed a pathology along the root of the canine only after the specimen had been cut.

What is thin-sectioning?

  • We make thin-sections of fossil bones and teeth so that we can study the fine, inner details of their hard tissues. These small details act as storybooks, preserving a lot of information about the biology of these animals while they were alive. As is easy to imagine, studying the biology of animals that lived millions of years ago can be challenging. We use the microstructure of fossil hard tissues to reveal aspects of their biology like growth rate, age and disease that otherwise would be inaccessible for us to study in these ancient animals.

Has an odontoma been found in the fossil record before?

  • This is not the first time an odontoma has been reported in the fossil record. Previous instances include: A Wooly mammoth from the Netherlands from the last glacial age (known as the Weichsel Glacial in Northern Europe, ca. 115,000-10,000 B.C.); Fossil red deer from France from 12,200-11,400 B.C.; Several recorded instances in archaeological material.
  • All reported instances, however, are relatively recent in the history of life on earth — to within the last 1 million years or so.

Is this the oldest occurrence of tumors in the fossil record?

  • No. There is a decisive case of cancer reported in a lower Carboniferous fish (300 million years ago), and a possible case of cancer in fossil fish from the Devonian (350 million years ago).
  • But this is the oldest reported case of an odontoma. See above question.

How do teeth form?

  • Teeth are derived from two major tissue layers, the outer epithelial layer that gives rise to enamel and an ectomesenchyme layer that gives rise to dentine and pulp.
  • Odontomas arise when there are developmental anomalies involving both the epithelial and ectomesenchymal tissues. These anomalies give rise to tooth-like structures that have enamel, cementum, dentine and pulp in their normal anatomical relationships.

What did we learn? What are the implications?

  • This is the oldest occurrence of odontoma in a mammal relative. Odontoma has remained relatively unchanged for 255 million years.
  • Paleontology can contribute to medicine by shedding light on the history of disease.

Acknowledgements

  • Laurent Nampunju and Anthony Tibaijuka (Antiquities Division, Ministry of Natural Resources and Tourism) for assistance with fieldwork in Tanzania.
  • Field team for helping to collect the fossil (Ken Angielczyk, Sterling Nesbitt, Roger Smith, Linda Tsuji).
  • Oral Biology group at the University of Washington for helpful discussions.
  • Royal Ontario Museum histology lab for use of thin section and imaging equipment.

Grant support

National Geographic Society (NGS 7787-05) to C. Sidor (for fieldwork to collect fossils)
National Science Foundation (DBI 0306158) to Ken Angielczyk, Field Museum of Natural History, Chicago (for fieldwork to collect fossils)
National Science Foundation (EAR 1337569) to C. Sidor (for research and analysis)

For additional information, contact Christian Sidor at [email protected] and Megan Whitney at [email protected]

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