New report spotlights breast tumor "evolution"

NEW YORK (Reuters Health) - As cancer progresses there can be "significant evolution" in malignant tissue, new research shows.

The findings suggest looking at primary tumor tissue may be a more precise way to spot tumor-initiating mutations than looking at metastatic cell lines, note Dr. Samuel Aparicio of the BC Cancer Agency in Vancouver and his colleagues.

Dr. Aparicio and his team examined genetic material from an estrogen-receptor-alpha-positive lobular breast tumor and from a metastasis of that tumor that occurred nine years later. They report their findings in the October 8th issue of Nature.

The researchers sequenced the genome and transcriptome of the metastasis, ultimately identifying 32 non-synonymous coding somatic point mutations. Five of the 32 mutations were found in the primary tumor, six were identified at lower frequencies, 19 were not found at all, and two were undetermined. The researchers also identified two new RNA editing events from their analysis of the genome and transcriptome of the metastasis.

It is not clear, Dr. Aparicio and his colleagues indicate, whether the 19 new mutations were a result of radiation therapy or "innate tumor progression."

Most analysis of coding mutations in breast cancer has been done in estrogen-receptor-positive disease, and has looked at metastatic cell lines or samples, the researchers note. These studies have "suggested the presence of large numbers of passenger events as well as drivers," they write.

"Our results show the importance of sequencing samples of tumor cell populations early as well as late in the evolution of tumors, and of estimating allele frequency in tumor genomes," they add. "Our observations suggest that the sequencing of primary breast cancers and pre-invasive malignancy may reveal significantly fewer candidates for tumor initiating mutations."

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