Genomic copy number alterations as predictive markers of systemic recurrence in breast cancer

Abstract

We tried to establish models that predict systemic recurrence in breast cancer by selecting marker clones with DNA copy number alterations (CNAs) using an array comparative genomic hybridization (CGH). Array CGH containing 4,044 human bacterial artificial chromosome clones was used to assess CNAs in 62 primary breast cancer tissues from 31 patients with systemic recurrence within 5 years after surgery and clinicopathologically well matched 31 patients who had no evidence of disease for at least 5 years. Fourteen significant clones (11 clones showing gain and 3 showing loss) were identified by systemic recurrence-free survival (SRFS) analysis and 23 significant clones (17 clones showing gain and 6 showing loss) identified by v 2 test and FDR test were selected as predictive markers of systemic breast cancer recurrence. The significant CNAs were found in the chromosomal regions of 5p15. 33, 11q13.3, 15q26.3, 17q25.3, 18q23 and 21q22.3 with gain and 9p12, 11q24.1 and 14q32.33 with loss. We devised 2 prediction models for the systemic recurrence of breast cancer based on the 14 clones and the 23 clones, respectively. The survivals of the patients were significantly separated according to the scores from each model at the optimal cut off values in SRFS and overall survival analysis. We found candidate clones and genes of which CNAs were significantly associated with systemic recurrence of breast cancer. The devised prediction models with these clones were effective at differentiating the recurrence and nonrecurrence. ' 2008 Wiley-Liss, Inc.Key words: array CGH; copy number alteration; breast cancer; systemic recurrence; predictive marker Many breast cancer patients share clinicopathological characteristics, such as, age, pathologic features, stage and so forth. However, despite the similar treatments used, breast cancer recurs in some patients but not in others. The recurrence of breast cancer is generally classified into 3 categories, i.e., local, regional and systemic recurrence, and of these, systemic recurrence is most closely related with survival rate. Although clinicians do their best to treat recurred patients using chemotherapy, hormonal therapy, radiation therapy and surgical options, the results of these treatments are generally poor.Several prognostic models have devised based on clinicopathological factors, such as, the St. Gallen criteria, 1 the National Institutes of Health Consensus Guidelines, 2 the Nottingham Prognostic Indicator 3 and Adjuvant Online, 4 but these have many limitations in terms of predicting systemic recurrence. There is an urgency to identify patients that require radical treatment because they have a high risk of recurrence, and conversely to identify those with a low risk of recurrence, but it is difficult to precisely predict systemic recurrence. At the present time, little is known of the factors correlated with systemic recurrence in breast cancer, despite the enormous amount of research conducted.Recently, microarray technology has enabled investigators to do undertake who...

Loss of 3p26.3 is an independent prognostic factor in patients with oral squamous cell carcinoma

“…In the present study, we applied A-CGH to Loss of 3p26.3 is an independent prognostic factor in patients with oral squamous cell carcinoma Analysis of A-CGH data. Data analysis was performed according to previous reports using the MAC array Karyo 4K (23,24). Spots with fluorescent intensity that was too low or too high to be analyzed were excluded from the analysis.…”

Characterization of amplification patterns and target genes on the short arm of chromosome 7 in early-stage lung adenocarcinoma

“…No patients had received pre-operative chemotherapy or radiation. This study was reviewed and approved by the Institutional Characterization of amplification patterns and target genes on the short arm of chromosome 7 in early-stage lung adenocarcinoma Preparation of DNA targets, labeling, hybridization, washing, staining and scanning was conducted according to the manufacturer's instructions (Macrogen, Seoul, Korea) (8)(9)(10)(11)(12)(13). Briefly, arrays were pre-hybridized with salmon sperm DNA to block repetitive sequences in the BACs.…”

Short Communication Significance of linkage disequilibrium heterogeneous patterns in the 21q22.3 region for mapping 21 trisomy individuals

“…This is true for the chromosome 21q region, where diverse recombination rates are observed and which contains the Down syndrome critical region (DSCR), located from 21q22.2 to 21q22.3 (Antonarakis et al, 2004). In addition to be related to Down syndrome, DSCR is of interest as some genes within this region have been associated with cancer (Hwang et al, 2008), diabetes (Concannon et al, 2008), and other disorders.…”