The Tumor That Grows Teeth

Watch

1. My ovary tumor grows teethyoutube.com/shorts/zf0GQxCVDcI

Word of the day

Teratoma (ter-uh-TOH-muh). A tumor made up of different types of tissue. A dermoid cyst is a mature cystic teratoma.

• Terabyte starts with tera-, from the same Greek word, téras. In units of measure, tera- means one trillion.
• Doctors use -oma in many tumor names, like melanoma and carcinoma.

Bonus words. Dermoid (from derm-, “skin,” and -oid, “like”) means skinlike. Homozygous (from homo-, “same”) describes a matching pair of alleles or markers. Heterozygous (from hetero-, “different”) describes a mixed pair.

Predict

1. In 1990, Urvashi Surti’s team compared chromosome markers near the centromere in dermoid cysts with the same markers in each patient’s healthy tissue. They counted only markers where the patient carried a heterozygous pair. A cyst grown from an ordinary body cell by mitosis would keep that pair heterozygous. Make a guess before you read the paper. What percent of these dermoid cysts do you think carried a homozygous pair at those markers? Give your reason in one sentence.

   Hint. In the video, Raven says a dermoid cyst starts from an egg that begins dividing on its own. Think about what meiosis does to each chromosome pair.

Read the paper

Surti, Hoffner, Chakravarti and Ferrell, “Genetics and biology of human ovarian teratomas. I. Cytogenetic analysis and mechanism of origin,” American Journal of Human Genetics, 1990. The paper is free to read as scanned pages.

The team studied 102 mature ovarian teratomas, the tumors also called dermoid cysts, from patients at Magee-Womens Hospital in Pittsburgh. Of the 102, 95 had a 46,XX karyotype. For each cyst, the team scored chromosome heteromorphisms, visible differences in size and staining near the centromeres, in the cyst and in the patient’s own normal tissue. A marker is informative when the patient’s two copies differ, and 13 cysts had no informative marker. The table gives the counts from the paper’s Results.

Counts from the paper’s Results

1. The counts table gives 58 homozygous and 31 heterozygous cysts out of 89 informative cysts. What percent of informative dermoid cysts were homozygous at the centromere markers? And why does that percent use 89 cysts instead of all 102?

   Hint. Fill in the last column first. A marker can only reveal a change when the patient’s two copies differ.

2. Mitosis, the division that copies body cells, keeps both chromosomes of each pair. Meiosis I, the first division on the way to an egg, separates the two chromosomes of each pair. What do the 58 homozygous cysts tell you about the cell each cyst started from, and how does that fit Raven’s claim in the video that the egg “starts dividing on its own”?

   Hint. Ask which kind of division could leave a cell with two matching copies where the patient carries two different ones.

3. The other 31 informative cysts stayed heterozygous at the centromere, like the patient. Surti’s team concluded that these cysts also came from germ cells, ones whose chromosome pairs never separated. Do the 31 heterozygous cysts weaken the germ cell explanation? What can centromere markers alone tell you about these cysts, and what can’t they tell you?

   Hint. Compare the centromere result you would expect from an ordinary body cell and from a germ cell whose pairs never separated.

4. Surti’s team ends the paper by describing ovarian teratomas as germ cells that begin embryonic differentiation without input from a father’s genome, giving a disorganized mix of mature tissues. In 2004, Tomohiro Kono’s team made Kaguya, a mouse with two sets of maternal chromosomes, one from an immature egg and one from a fully grown egg. The immature egg came from a mouse with a deletion in the H19 gene. Why does differentiation without a father’s genome make tissues but not an organized embryo? What does Kaguya the mouse add to that explanation?

   Hint. Think about genomic imprinting, and about which genes the H19 deletion helped express at the right levels.

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