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Alternate Chromosome 17 Genes Detect True HER2 Status

Three alternative chromosome 17 genes determine true HER2 status in breast cancer with polysomy 17

WEDNESDAY, Sept. 28 (HealthDay News) -- For patients with breast cancer and polysomy 17, the true gene status of human epidermal growth factor receptor 2 (HER2) can be effectively determined by use of additional chromosome 17 fluorescent in situ hybridization (FISH) studies for Smith-Magenis syndrome (SMS), retinoic acid receptor alpha (RARA), and tumor protein p53 (TP53) genes, rather than the HER2-to-centromeric probe (CEP17) ratio, according to a study published online Sept. 26 in the Journal of Clinical Oncology.

Chun Hing Tse, M.D., from PhenoPath Laboratories in Seattle, and colleagues investigated whether the use of the alternative chromosome 17 reference genes can accurately assess true HER2 gene status. Additional chromosome studies were performed using probes for SMS, RARA, and TP53 genes in 171 patients with breast cancer who had HER2 FISH and whose mean CEP17 copy numbers were more than 2.6. The eusomic copy number was used to evaluate the revised HER2-to-chromosome-17 ratio with the eusomic gene locus as the reference.

The investigators found that, based on use of alternative chromosome 17 reference gene probes, 43.9 percent of the 132 cases classified as nonamplified on the basis of HER2:CEP17 ratios were scored as amplified. In addition, 92.9 percent of the 14 cases scored as equivocal were reclassified as amplified by using alternative chromosome 17 reference gene probes. For patients with a mean HER2 copy number of 4 to 6, 47.7 and 4.7 percent had their HER2 gene status upgraded from nonamplified to amplified and from equivocal to amplified, respectively.

"Additional FISH studies that use probes to the SMS, RARA, and TP53 genes are an effective way to determine the true HER2 amplification status in patients with polysomy 17," the authors write.

Several of the study authors disclosed financial relationships with PhenoPath Laboratories.

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