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Allelic Losses of Loci at 3p25.1, 8p22, 13q12, 17p13.3, and 22q13 Correlate with Postoperative Recurrence in Breast Cancer¹

Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, 211-8533 [A. H., M. E., M. T., Y. U.]; Department of Surgery and Pathology, Cancer Institute, Toshima-ku, 170-8455 [Y. U., M. Y., F. K., F. A., G. S.]; Department of Surgery, Daini Hospital, Tokyo Women’s Medical University, Arakawa-ku, Tokyo 116-8567 [A. H., Y. U., S. H., T. K.]; Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639 [Y. N.], Japan

We previously defined 18 chromosomal regions in which frequent allelic losses were observed in breast cancers (T. Sato et al., Cancer Res., 50: 7184–7189, 1990; Y. Harada et al., Cancer (Phila.), 74: 2281–2286, 1994; I. Ito et al., Br. J. Cancer, 71: 438–441, 1995; K. Tsukamoto et al., Cancer (Phila.), 78: 1929–1934, 1996; S. Matsumoto et al., Genes Chromosomes Cancer, 20: 268–274, 1997; T. Yokota et al., Jpn. J. Cancer Res., 88: 959–964, 1997; K. Tsukamoto et al., Cancer (Phila.), 82: 317–322, 1998; A. Iida et al., Genes Chromosomes Cancer, 21: 108–112, 1998; K. Fukino et al., Genes Chromosomes Cancer, 24: 345–350, 1999; T. Yokota et al., Cancer (Phila.), 85: 447–452, 1999; Y. Utada et al., Jpn. J. Cancer Res., 91: 293–300, 2000). To identify specific allelic losses that might correlate with postoperative recurrence, we examined tumors from a cohort of 504 breast cancer patients, who were followed clinically for 5 years postoperatively, for allelic losses of 18 microsatellite markers. Patients whose tumors had lost an allele at 3p25.1, 8p22, 13q12, 17p13.3, or 22q13 had significantly higher risks of recurrence than those whose tumors retained both alleles at those loci; at 3p25.1, the 5-year recurrence rate was 27% among patients with losses versus 18% with retention (P = 0.0131); at 8p22, 27% versus 14% (P = 0.0129); at 13q12, 28% versus 15% (P = 0.0109); at 17p13.3, 27% versus 20% (P = 0.0482); and at 22q13, 29% versus 20% (P = 0.0477). These data indicate that loss of heterozygosity at any one of these five specific loci is a significant predictor of postoperative recurrence among patients who have undergone surgery for breast cancer. These allelic losses can serve as negative prognostic indicators to guide postoperative management of patients.

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