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DNA Changes in Stromal Cells Linked to Breast Tumor Grade

Researchers use whole genome technique to identify DNA regions in stromal cells surrounding tumors

TUESDAY, May 15 (HealthDay News) -- Genetic markers found in the stromal and epithelial cells surrounding primary sporadic breast cancers are associated with tumor grade, metastases and other clinicopathological features, such as the presence of progesterone receptors, according to a report in the May 16 issue of the Journal of the American Medical Association.

Charis Eng, M.D., Ph.D., of the Cleveland Clinic Genomic Medicine Institute in Ohio, measured loss of heterozygosity and allelic imbalances by whole genome genotyping in stromal and epithelial cells from 220 primary sporadic invasive breast carcinomas.

The investigators found two markers on chromosome 14 in epithelial cells that were associated with progesterone-receptor expression, and genomic instability on seven chromosomes (1, 2, 5, 11, 18, 20, 22) in stromal cells that were linked to either tumor grade or the presence of lymph node metastases. The "hot spots" included regions near the ATM and TP53 genes, but did not include the HER2 gene, perhaps because of low resolution.

"Genetic changes acquired in the stroma adjacent to transformed epithelial cells contribute an additional dimension of progression modulation beyond that contributed by the carcinoma cells themselves. The combination of stromal and epithelial genetic changes produces a greater range of outcome scenarios than can otherwise be explained by carcinoma cell genotype alone," the authors conclude. The data should be validated in larger trials with longer follow-ups, they add.

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