CCND1 and ZNF217 gene amplification is equally frequent in BRCA1 and BRCA2 associated and non-BRCA breast cancer
Abstract:
Breast cancer associated with BRCA1 and BRCA2 gene mutations differs from non-BRCA tumors in several respects. We determined whether there was any difference in CCND1 (11q13) and ZNF217 (20q13) gene amplification with respect to BRCA status. Of 40 breast cancer samples examined, 15 and 9 were from BRCA1 and BRCA2 mutation carriers, respectively, and 16 from patients without mutation. Fluorescence in situ hybridization showed that eight tumors exhibited CCND1 amplification (20%; 3 BRCA1, 3 BRCA2, 2 non-BRCA). ZNF217 amplification was observed in three of 38 cases (8%; 2 BRCA1, 1 non-BRCA). There was no significant difference in CCND1 and ZNF217 amplification between BRCA1, BRCA2 and non-BRCA tumors. CCND1 amplification was associated with decreased disease-free (P = 0.045) and overall survival (P = 0.015). BRCA1 tumors with CCND1 amplification were estrogen receptor negative, in contrast to CCND1 amplified BRCA2 and non-BRCA tumors, suggesting that concurrent CCND1 amplification and estrogen and progesterone receptor negativity may predict germline BRCA1 gene mutation. All ZNF217 amplified tumors were of the medullary histological type (P = 0.002). There was no statistical correlation between CCND1 and ZNF217 amplification and estrogen receptor, progesterone receptor, and ERBB2 expression and TNM classification. CCND1 amplification did not correlate with EGFR expression.