Addressing the Elephant in the Room in Cancer Genetic

Researchers from Harvard Medical School have predicted that many more tumor suppressor and oncogenes have a combined effect on the development of disease than originally thought, concluding that cancer is even more complex than imagined.

In a paper published last month in the journal Cell, the team—led by Medical School professor of genetics Stephen J. Elledgeaddressed the impact of aneuploidy, an extra or missing chromosome in an individual’s cells, on cancer development.


While aneuploidy is a very common abnormality, most aneuploidies are lethal.

Aneuploidy has been observed in cancer patients for a while, but Elledge said that “aneuploidy was the elephant in the room.” He explained that the oncogene revolution brought point mutations to the attention of scientists and research has been focused on simpler targets in the last several decades.

Using a computational method that they devised, Elledge’s team analyzed mutations in tumors for tumor suppressor genes and oncogenes to identify mutation patterns that give rise to an oncogenic state.

The paper, titled “Cumulative Haploinsufficiency and Triplosensitivity Drive Aneuploidy Patterns and Shape the Cancer Genome,” reported that many more factors can drive the development of cancer, such as avoiding apoptosis, or programmed cell death, escaping immune response, avoiding differentiation, and sustaining proliferation.

In addition, the researchers found that contribution of weak drivers can sum up to correspond to the effect of a more potent driver.


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