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.

Stiff stroma increases breast cancer risk by inducing the oncogene ZNF217

“…To clarify whether and how the low levels of miR-203 in the epithelium of the high-density, stiff breast tissue could increase breast cancer risk, we used online tools (miRWalk2.0, miRTarBase) (55,56) to generate a list of predicted miR-203 targets, and identified several previously implicated in breast cancer for further scrutiny (Supplemental Table 4). ZNF217 was selected for further investigation because of its known role in enhancing MEC and breast cancer cell growth, expanding breast progenitor frequency and promoting a mesenchymal transition, and its demonstrated impact on breast cancer progression and aggression (57)(58)(59). Furthermore, ZNF217 was previously validated as a miR-203 target in colon cancer cells (60).…”

A functional interplay between ZNF217 and Estrogen Receptor alpha exists in luminal breast cancers

“…ZNF217 thus allows the re‐stratification of patients with ER+/Luminal breast cancers which are considered to be cancers with a good prognosis where no other biomarkers are currently available and widely used. In breast tumours, amplification at the ZNF217 locus has been reported (for review, Quinlan et al., 2007), but ZNF217 amplification did not demonstrate any correlation/association with ER status (Letessier et al., 2006; Plevova et al., 2010), nor with PR‐positive status in breast cancers (Letessier et al., 2006; Plevova et al., 2010). Therefore, the expression levels and prognostic value of ZNF217 mRNA levels in ER+/Luminal breast tumours is more likely not to be attributable to any amplification at the ZNF217 locus, and most likely more informative than investigating ZNF217 amplification only.…”

The dark side of ZNF217, a key regulator of tumorigenesis with powerful biomarker value

“…This region also contains several oncogenes thought to confer selective advantages to cancer cells. Increased copy numbers of ZNF217 have been reported in various tumors (frequency is variable among tumors) [ 5 - 7 ] and linked to poor outcome in some studies [ 8 - 11 ].…”