Molecular trigger for breast cancer development identified

In what may turn out to be a long-missing piece in the puzzle of breast cancer, Harvard Medical School researchers have identified the molecular sparkplug that ignites cases of the disease currently unexplained by the classical model of breast-cancer development.

"Our work demonstrates that estrogen can directly induce genomic rearrangements that lead to cancer, so its role in breast cancer development is both that of a catalyst and a cause," said study first author Jake Lee, a former research fellow in the Park lab who is now a medical oncology fellow at Memorial Sloan Kettering Cancer Center.

One such chromosomal scramble can occur when a chromosome breaks, and a second copy of the broken chromosome is made before the break gets fixed. Cancer experts can often identify this particular aberration in tumor samples by using genomic sequencing. Yet, a portion of breast cancer cases do not harbor this mutational pattern, raising the question: What is causing these tumors?

Lee and Park realized they had stumbled upon a new mechanism by which a"disfigured" chromosome is generated and then fractured to fuel the mysterious breast cancer cases.When the researchers zoomed onto the hot spots of cancer-gene activation, they noticed that these areas were curiously close to estrogen-binding areas on the DNA.

As the cells mended their broken DNA, they initiated a repair chain that resulted in the same genomic rearrangement Lee and Park had discovered in their genomic analyses.

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